Eric E. Bouhassira

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Full Name
Eric E. Bouhassira
Profile Image URL
https://assets.montefioreeinstein.org/profiles/images/4981-eric-bouhassira.jpg
Type
Faculty
Expert
First Name
Eric
Last Name
Bouhassira
Faculty ID
4981
Patient Type
Adult
Department
einstein-dept-cell-biology
einstein-dept-medicine
einstein-dept-oncology
Email
eric.bouhassira@einsteinmed.edu
Phone
718-430-2188
Titles
Type
Academic
Department
Department of Cell Biology
Department Link
Rank
Professor
Tags
me-patientcare-cancer-clinical-gastrointestinal
me-patientcare-cancer-research-stem-cell-cancer-biology
Type
Academic
Department
Department of Medicine
Department Link
Rank
Professor
Division
Oncology & Hematology
Type
Academic
Department
Department of Oncology
Rank
Professor
Division
Hematology
Type
Administrative
Title
Ingeborg and Ira Leon Rennert Professor of Stem Cell Biology and Regenerative Medicine
Locations
Is Primary
Off
Type
Academic
Location (Address, State, City, Zip)
Not used, will be deleted
Coordinates
POINT (-73.8459022 40.8504961)
Building
Ullmann Building
Room
903A
Address Line 1
Albert Einstein College of Medicine
Address Line 2
Jack and Pearl Resnick Campus
Address Line 3
1300 Morris Park Avenue
City
Bronx
State
NY
Zip
10461
Location Title
Albert Einstein College of Medicine
Professional Interests

<p>Dr. Eric E. Bouhassira joined the Albert Einstein College of Medicine in 1990. He began studying human embryonic stem cells in 2001. He is director of the medical school's Center for Human Embryonic Stem Cell Research and professor of medicine and of cell biology. Dr. Bouhassira's research focuses on developing hematopoietic (blood forming) stem cells that can differentiate into red blood cells, T cells, platelets, and all other cell types that comprise blood. This work could potentially aid patients needing transfusions and also save lives by expanding the immunology diversity of hematopoietic stem cells available for transplant. Dr. Bouhassira is also interested in epigentic regulation in the erythoid and hematopoeitic lineag with a focus on DNA replication and DNA methylation. Dr. Bouhassira received his B.S., M.S., and Ph.D. degrees from the Universit&eacute; Pierre et Marie Curie in Paris, France. Dr. Bouhassira also holds the Ingeborg and Ira Rennert Chair in Stem Cell Biology and Regenerative Medicine.</p>
<p><strong>Current Clinical Protocols</strong></p>
<ol>
<li>In vitro red blood cell production</li>
<li>Feasibility pilot study of therapies for sickle cell disease and Thalassemia</li>
<li>Quartet sequencing and genome phasing</li>
</ol>

Research Areas
Pluripotent stem cells, erythroid differentiation, red blood cells, gene therapy, hemoglobinopathies, genome modification, TTP, hemophilia A
Specialties
Expert Tags
Areas of Expertise
Bioinformatics
Embryonic stem cells
Gene therapy
Globin genes
Hematopoiesis
Red blood cells
Sickle cell anemia
Thalassemia
Transcriptional regulation
Expert Summary

<p class="MsoNormal" style="line-height: 15.6pt;">Dr. Bouhassira&rsquo;s work focuses on prompting human embryonic stem cells to develop into hematopoietic (blood-forming), as well as stem cells, and into red blood cells. This work could potentially help patients needing transfusions and save lives by expanding the production of customized cells that could be transplanted without risk of rejection. The cells produced by Dr. Bouhassira can also be used to deliver therapeutic proteins to the circulatory system.&nbsp;</p>
<p class="MsoNormal" style="line-height: 15.6pt;">Dr. Bouhassira&rsquo;s research also aims to find cures for sickle cell disease by developing novel gene therapy strategies.</p>

CHAM Provider
Off
Professional Title
Ph.D.
Selected Publications

<p class="MsoNormal"><strong style="mso-bidi-font-weight: normal;">&nbsp;</strong> <strong><span style="font-family: Arial, sans-serif;">Complete bibliography:</span></strong>&nbsp;<span style="background-image: initial; background-position: initial; background-size: initial; background-repeat: initial; background-attachment: initial; background-origin: initial; background-clip: initial; font-size: 11.5pt; font-family: Helvetica, sans-serif; color: #212121;">&nbsp;</span><a href="https://www.ncbi.nlm.nih.gov/myncbi/14gVia2i54M5O/bibliography/public/"… style="font-size: 11.5pt; font-family: Helvetica, sans-serif; color: #4c2c92; background-image: initial; background-position: initial; background-size: initial; background-repeat: initial; background-attachment: initial; background-origin: initial; background-clip: initial;">https://www.ncbi.nlm.nih.gov/myncbi/14gVia2i54M5O/bibliography/public/<…;
<p class="MsoNormal" style="text-indent: .25in;"><strong style="mso-bidi-font-weight: normal;"><span style="background: lightgrey; mso-highlight: lightgrey;">Research areas:</span></strong></p>
<p class="MsoNormal" style="text-indent: .25in;"><strong style="mso-bidi-font-weight: normal;"><span style="background: lightgrey; mso-highlight: lightgrey;">Development of methods to produce cultured red blood cells from hematopoietic stem cells and from pluripotent stem cells.</span></strong></p>
<p class="MsoNormal"><span style="text-align: justify; text-indent: 0.25in;">Progress in cell culture methods has open up the possibility of manufacturing red blood cells (RBCs) for transfusion. We have developed methods to produce large number of red blood cells from hematopoietic stem cells and from pluripotent stem cells. Using detailed analysis of globin chain expression, we were the first to demonstrate that differentiation of hESCs and iPSCs into erythroid cells faithfully recapitulates the embryonic and fetal stages of human erythropoiesis but do not yield red blood cells with an adult phenotype. We also demonstrated that fetal stage erythroid cells derived from pluripotent cells can enucleate </span><em style="text-align: justify; text-indent: 0.25in;">in vitro</em><span style="text-align: justify; text-indent: 0.25in;">.</span>Since these early studies, observations that cells produced from pluripotent cells are developmentally immature have been made in many other lineages, by others. Finding methods to produce developmentally mature cells from pluripotent stem cells has become a central focus of many labs including my own. We recently obtained NIH funding to apply our advanced culture methods and translate our results into a commercial product by developing a panel of IPSC lines from patients carrying very rare blood groups that can be used as universal donor for transfusion and as reagent RBCs that will be used to type antibodies in allo-immunized patients with sickle cell disease.</p>
<p class="MsoListParagraph" style="margin-left: .25in; text-align: justify; text-indent: -.25in; mso-list: l5 level1 lfo5;"><!-- [if !supportLists]--><span style="mso-bidi-font-size: 11.0pt; mso-fareast-font-family: Arial; mso-bidi-font-family: Arial;"><span style="mso-list: Ignore;">1.<span style="font: 7.0pt 'Times New Roman';">&nbsp;&nbsp;&nbsp; </span></span></span><!--[endif]--><span lang="FR" style="mso-bidi-font-family: Arial; mso-ansi-language: FR;">Olivier EN, Qiu C, Velho M, Hirsch RE, Bouhassira EE. </span><strong style="mso-bidi-font-weight: normal;"><span style="mso-bidi-font-family: Arial;">Large-scale production of embryonic red blood cells from human embryonic stem cells.</span></strong> <span style="mso-bidi-font-size: 11.0pt; mso-bidi-font-family: Arial;">Exp Hematol. 2006 Dec;34(12):1635-42.</span> <span style="mso-bidi-font-size: 11.0pt; mso-bidi-font-family: Arial;">PMID: 17157159 <u>Cited by 161</u></span>&nbsp;</p>
<p class="MsoListParagraph" style="margin-left: .25in; text-align: justify; text-indent: -.25in; mso-list: l5 level1 lfo5;"><!-- [if !supportLists]--><span style="mso-fareast-font-family: Arial; mso-bidi-font-family: Arial;"><span style="mso-list: Ignore;">2.<span style="font: 7.0pt 'Times New Roman';">&nbsp;&nbsp;&nbsp; </span></span></span><!--[endif]--><span lang="FR" style="mso-ansi-language: FR;">Qiu C, Olivier EN, Velho M, Bouhassira EE. </span><strong style="mso-bidi-font-weight: normal;">Globin switches in yolk sac primitive and fetal definitive RBCs produced from human embryonic stem cells</strong>. Blood. 2008; 111(4):2400-8. PMID: 18024790 <u>Cited by 154</u></p>
<p class="MsoListParagraph" style="margin-left: .25in; text-align: justify; text-indent: -.25in; mso-list: l5 level1 lfo5;"><!-- [if !supportLists]--><span style="mso-bidi-font-size: 9.0pt; mso-fareast-font-family: Arial; mso-bidi-font-family: Arial;"><span style="mso-list: Ignore;">3.<span style="font: 7.0pt 'Times New Roman';">&nbsp;&nbsp;&nbsp; </span></span></span><!--[endif]-->Wang K, Guzman AK, Yan Z, Zhang S, Hu MY, Hamaneh MB, Yu YK, Tolu S, Zhang J, Kanavy HE, Ye K, Bartholdy B, Bouhassira EE. <strong style="mso-bidi-font-weight: normal;">Ultra-High-Frequency Reprogramming of Individual Long-Term Hematopoietic Stem Cells Yields Low Somatic Variant Induced Pluripotent Stem Cells.</strong> <span style="mso-bidi-font-size: 9.0pt;">Cell Rep. 2019 Mar 5;26(10):2580-2592.e7<span style="mso-spacerun: yes;">&nbsp; </span>PMID: 30840883 <u>Cited by 2</u></span></p>
<p class="MsoListParagraph" style="margin-left: .25in; text-align: justify; text-indent: -.25in; mso-list: l5 level1 lfo5;"><!-- [if !supportLists]--><span style="mso-bidi-font-size: 11.0pt; mso-fareast-font-family: Arial; mso-bidi-font-family: Arial;"><span style="mso-list: Ignore;">4.<span style="font: 7.0pt 'Times New Roman';">&nbsp;&nbsp;&nbsp; </span></span></span><!--[endif]-->Olivier EN, Zhang S, Yan Z, Suzuka S, Roberts K, Wang K, Bouhassira EE. <strong style="mso-bidi-font-weight: normal;">RED, an Albumin-Free Robust Erythroid Differentiation Method to Produce Enucleated Red Blood Cells from Human Pluripotent and Adult Stem Cells. </strong><span style="mso-bidi-font-size: 11.0pt;">Exp Hematol. 2019 Jul;75:31-52.e15 </span><span style="mso-bidi-font-size: 11.0pt; font-family: 'Helvetica',sans-serif; mso-bidi-font-family: 'Times New Roman'; color: #212121; background: white;">PMID: 31176681</span></p>
<p class="MsoListParagraph" style="margin-left: .25in; text-align: justify; text-indent: -.25in; mso-list: l5 level1 lfo5;"><!-- [if !supportLists]--><span style="font-size: 9.0pt; mso-fareast-font-family: Arial; mso-bidi-font-family: Arial;"><span style="mso-list: Ignore;">5.<span style="font: 7.0pt 'Times New Roman';">&nbsp;&nbsp;&nbsp;&nbsp; </span></span></span><!--[endif]--><span lang="FR" style="mso-ansi-language: FR;">Olivier EN, Wang K, Grossman J, Mahmud N, Bouhassira EE. </span><strong style="mso-bidi-font-weight: normal;">Differentiation of Baboon (Papio anubis) Induced-Pluripotent Stem Cells into Enucleated Red Blood Cells.</strong> <span style="font-size: 9.0pt;">Cells. 2019 Oct 19;8(10).PMID: 31635069.</span></p>
<p class="MsoListParagraph" style="margin-left: .25in; text-align: justify; text-indent: -.25in; mso-list: l5 level1 lfo5;"><!-- [if !supportLists]--><strong style="mso-bidi-font-weight: normal;"><span style="background: lightgrey; mso-highlight: lightgrey;">Gene therapy for the hemoglobinopathies</span></strong></p>
<p class="MsoListParagraph" style="text-autospace: ideograph-numeric ideograph-other;"><strong style="mso-bidi-font-weight: normal;">&nbsp;</strong><span style="text-align: justify; text-indent: 0.25in;">Lentiviral based gene therapy for the hemoglobinopathies is coming of age. We have contributed to the field by studying at the basic science level the major causes of transgene silencing in erythroid cells. Using the RMCE method we have demonstrated that in eukaryotic cells, silencing is not primarily caused by integration near heterochromatin but rather by transcriptional interferences between the transgenes and neighboring sequences. By studying cassettes that were either devoid of any CpG dinucleotides, or that were pre-methylated prior to integration, we were able to demonstrate that DNA methylation is not necessary for silencing but that it confers an epigenetic memory.</span></p>
<p class="MsoNormal" style="text-align: justify; text-indent: .25in; text-autospace: ideograph-numeric ideograph-other;">We also demonstrated that inclusion of insulators in gene therapy cassettes was a double edged sword since these elements can prevent silencing and insertional mutagenesis at some genetic loci, but can also cause silencing and insertional mutagenesis at other locations. Some of these basic science findings were applied to design the gene therapy cassettes that were used, in collaboration with the Leboulch lab, to provide the first proof of principle in mice that gene therapy could be used to cure sickle cell disease. These vectors are currently tested by BlueBird therapeutics in human clinical trials that have had encouraging results.</p>
<p class="MsoNormal" style="margin-left: 13.5pt; text-indent: -.25in; mso-list: l4 level1 lfo1; mso-layout-grid-align: none; text-autospace: ideograph-numeric ideograph-other;"><!-- [if !supportLists]--><span style="mso-bidi-font-size: 11.0pt; mso-fareast-font-family: Arial; mso-bidi-font-family: Arial;"><span style="mso-list: Ignore;">1.<span style="font: 7.0pt 'Times New Roman';">&nbsp;&nbsp;&nbsp; </span></span></span><!--[endif]--><span style="mso-bidi-font-family: Arial;">Feng YQ, Warin R, Li T, Olivier E, Besse A, Lobell A, Fu H, Lin CM, Aladjem MI, Bouhassira EE. (2005): <strong style="mso-bidi-font-weight: normal;">The Human </strong></span><strong style="mso-bidi-font-weight: normal;"><span style="font-family: Symbol; mso-bidi-font-family: Arial;">b</span></strong><strong style="mso-bidi-font-weight: normal;"><span style="mso-bidi-font-family: Arial;">-Globin Locus Control Region Can Silence as Well as Activate Gene Expression</span></strong><span style="mso-bidi-font-family: Arial;">. </span><span style="mso-bidi-font-size: 11.0pt; mso-bidi-font-family: Arial;">Mol Cell Biol.25: (10):3864-74.</span> <span style="mso-bidi-font-size: 11.0pt; mso-bidi-font-family: Arial;">PMID: 15870261 <u>Cited by 44</u></span></p>
<p class="MsoNormal" style="margin-left: 13.5pt; text-indent: -.25in; mso-list: l4 level1 lfo1; mso-layout-grid-align: none; text-autospace: ideograph-numeric ideograph-other;"><!-- [if !supportLists]--><span style="mso-bidi-font-size: 11.0pt; mso-fareast-font-family: Arial; mso-bidi-font-family: Arial;"><span style="mso-list: Ignore;">2.<span style="font: 7.0pt 'Times New Roman';">&nbsp;&nbsp;&nbsp; </span></span></span><!--[endif]--><span style="mso-bidi-font-family: Arial;">Feng YQ, Desprat R, Fu H, Olivier E, Lin CM, Lobell A, Gowda SN, Aladjem MI, Bouhassira EE. (2006). <strong style="mso-bidi-font-weight: normal;">DNA methylation supports intrinsic epigenetic memory in mammalian cells. </strong></span><span style="mso-bidi-font-size: 11.0pt; mso-bidi-font-family: Arial;">PLoS Genet. </span><span lang="FR" style="mso-bidi-font-size: 11.0pt; mso-bidi-font-family: Arial; mso-ansi-language: FR;">2006 Epub 2006 Apr 28.</span> <span lang="FR" style="mso-bidi-font-size: 11.0pt; mso-bidi-font-family: Arial; mso-ansi-language: FR;">PMID: 16683039 <u>Cited by 75</u></span></p>
<p class="MsoNormal" style="margin-left: 13.5pt; text-indent: -.25in; mso-list: l4 level1 lfo1; mso-layout-grid-align: none; text-autospace: ideograph-numeric ideograph-other;"><!-- [if !supportLists]--><span style="mso-bidi-font-size: 11.0pt; mso-fareast-font-family: Arial; mso-bidi-font-family: Arial;"><span style="mso-list: Ignore;">3.<span style="font: 7.0pt 'Times New Roman';">&nbsp;&nbsp;&nbsp; </span></span></span><!--[endif]--><span style="mso-bidi-font-family: Arial;">Pawliuk R., KA Westerman, ME Fabry, E Payen, R Tighe, EE Bouhassira, SA Acharya, J Ellis, IM London, CJ Eaves, RK Humphries, Y Beuzard, RL Nagel, P Leboulch<span style="mso-spacerun: yes;">&nbsp; </span>(2001):<span style="mso-spacerun: yes;">&nbsp; </span><strong>Correction of sickle cell disease in transgenic mouse models by gene therapy.</strong> </span><span style="mso-bidi-font-size: 11.0pt; mso-bidi-font-family: Arial;">Science<span style="mso-spacerun: yes;">&nbsp; </span>294:2368-71. PMID: 11743206 <u>Cited by 574</u></span>&nbsp;</p>
<p class="MsoNormal" style="margin-left: 13.5pt; text-indent: -.25in; mso-list: l4 level1 lfo1; mso-layout-grid-align: none; text-autospace: ideograph-numeric ideograph-other;"><!-- [if !supportLists]--><span style="mso-bidi-font-size: 11.0pt; mso-fareast-font-family: Arial; mso-bidi-font-family: Arial;"><span style="mso-list: Ignore;">4.<span style="font: 7.0pt 'Times New Roman';">&nbsp;&nbsp;&nbsp; </span></span></span><!--[endif]--><span style="mso-bidi-font-size: 11.0pt; mso-bidi-font-family: Arial;">Boulad F, Maggio A, Xiuyan Wang X, Moi P, Acuto S, Kogel F, Takpradit A, Prockop S, Mansilla-Soto J, Cabriolu A, Odak A. Thummar K, Du F, Shen L, Raso s, Barone R, Di Maggio R, Pitrolo L, Giambona A, Mingoia M, Everett JK, Hokama P, Roche A, Cantu A, Adhikari H, Reddy S, Bouhassira EE, Mohandas N, Bushman FD, Rivi&egrave;re I, Sadelain M (2001) <strong>Lentiviral globin gene therapy with reduced-intensity conditioning in adults with &beta;-thalassemia: a phase 1 trial.<span style="mso-spacerun: yes;">&nbsp;&nbsp;</span></strong></span><span style="font-family: Arial, sans-serif; font-size: 10.5pt;">Nat Med. 2022 Jan;28(1):63-70.</span></p>
<p class="MsoNormal" style="margin-left: 13.5pt; text-indent: -.25in; mso-list: l4 level1 lfo1; mso-layout-grid-align: none; text-autospace: ideograph-numeric ideograph-other;"><strong style="mso-bidi-font-weight: normal;"><span style="background: lightgrey; mso-highlight: lightgrey;">Development of Recombinase-Mediated Cassette Exchange and safe harbor concept</span></strong></p>
<p class="MsoNormal" style="text-align: justify; text-indent: .25in; text-autospace: ideograph-numeric ideograph-other;">Lentiviral transduction, stable transfection and transgenesis results in random integration of transgenes which leads to positive or negative position-effects. Position-effects greatly complicate gene therapy as well as the interpretation of most stable transfection or transduction experiments. To eliminate these problems, we have developed RMCE, a method that allows site-specific integration of cassettes at predetermined chromosomal locations in mammalian cells. We used the method extensively to better understand the molecular basis of position-effects in erythroid cells (see above). Many other labs, all over the world, have adopted RMCE, and adapted it to many cell types and many organisms. Over 500 studies that take advantage of RMCE have been published.</p>
<p class="MsoNormal" style="text-align: justify; text-autospace: ideograph-numeric ideograph-other;"><span style="mso-tab-count: 1;">&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span>The use of the RMCE led us to develop the concept of safe harbors as an efficient method to perform gene therapy safely and cost efficiently, without having to design and test novel vector or gene editing strategy for every mutation in every defective human gene. We demonstrated the concept by correcting alpha-thalassemia in iPSCs by targeting constructs to the AAVS1.</p>
<p class="MsoNormal" style="margin-left: .25in; text-indent: -.25in; mso-list: l0 level1 lfo2; mso-layout-grid-align: none;"><!-- [if !supportLists]--><span style="mso-bidi-font-size: 11.0pt; mso-fareast-font-family: Arial; mso-bidi-font-family: Arial;"><span style="mso-list: Ignore;">1.<span style="font: 7.0pt 'Times New Roman';">&nbsp;&nbsp;&nbsp; </span></span></span><!--[endif]--><span style="mso-bidi-font-family: Arial;">Bouhassira EE., K Westerman, P Leboulch: (1997) <strong>Transcriptional Behavior Of LCR Elements Integrated At The Same Chromosomal Locus By RMCE.</strong> </span><span style="mso-bidi-font-size: 11.0pt; mso-bidi-font-family: Arial;">Blood, 90: 3332-3244.</span> <span style="mso-bidi-font-size: 11.0pt; mso-bidi-font-family: Arial;">PMID: 9345015 <u>Cited by 177</u></span></p>
<p class="MsoNormal" style="margin-left: .25in; text-indent: -.25in; mso-list: l0 level1 lfo2; mso-layout-grid-align: none;"><!-- [if !supportLists]--><span style="mso-bidi-font-size: 11.0pt; mso-fareast-font-family: Arial; mso-bidi-font-family: Arial;"><span style="mso-list: Ignore;">2.<span style="font: 7.0pt 'Times New Roman';">&nbsp;&nbsp;&nbsp; </span></span></span><!--[endif]--><span style="mso-bidi-font-family: Arial;">Feng YQ, Seibler J, Alami R, Eisen A, Fiering SN, Bouhassira EE: (1999) <strong>Site-Specific Chromosomal Integration In Mammalian cells: Highly Efficient CRE Recombinase-Mediated Cassette Exchange.</strong> </span><span style="mso-bidi-font-size: 11.0pt; mso-bidi-font-family: Arial;">J. Mol. Biol. 292 (4): 779-785. PMID: 10525404 <u>Cited by 249</u></span></p>
<p class="MsoNormal" style="margin-left: .25in; text-indent: -.25in; mso-list: l0 level1 lfo2; mso-layout-grid-align: none;"><!-- [if !supportLists]--><span style="font-size: 9.0pt; mso-fareast-font-family: Arial; mso-bidi-font-family: Arial;"><span style="mso-list: Ignore;">3.<span style="font: 7.0pt 'Times New Roman';">&nbsp;&nbsp;&nbsp;&nbsp; </span></span></span><!--[endif]--><span style="mso-bidi-font-family: Arial;">Chang CJ and Bouhassira EE. <strong style="mso-bidi-font-weight: normal;">Zinc-finger nuclease mediated correction of &alpha;-thalassemia in iPS cells</strong>. Blood. 2012; Nov 8;120(19):3906-14. PMID: 23002118 <u>Cited by 100</u></span></p>
<p class="MsoNormal" style="margin-left: .25in; text-indent: -.25in; mso-list: l0 level1 lfo2; mso-layout-grid-align: none;"><!-- [if !supportLists]--><strong style="mso-bidi-font-weight: normal;"><span style="background: lightgrey; mso-highlight: lightgrey;">Molecular basis of Thrombotic Thrombocytopenic Purpura</span></strong></p>
<p class="MsoNormal" style="text-autospace: ideograph-numeric ideograph-other;">In collaboration with Dr. Han-Mou Tsai we have demonstrated that ADAMTS13 is responsible for congenital TTP, that auto-antibody resistant forms of the protein could be generated, that ADMTS13 is expressed predominantly in stellate cells, and we have explored some of the molecular mechanisms associated with low levels of ADAMTS13 expression in human population.<span style="mso-spacerun: yes;">&nbsp;</span></p>
<p class="MsoListParagraph" style="margin-left: 31.5pt; text-indent: -.25in; mso-list: l2 level1 lfo4; mso-layout-grid-align: none; text-autospace: ideograph-numeric ideograph-other;"><!-- [if !supportLists]--><span style="mso-bidi-font-size: 11.0pt; mso-fareast-font-family: Arial; mso-bidi-font-family: Arial;"><span style="mso-list: Ignore;">1.<span style="font: 7.0pt 'Times New Roman';">&nbsp;&nbsp;&nbsp; </span></span></span><!--[endif]--><span style="mso-bidi-font-family: Arial;">Levy GG, Nichols WC, Lian EC, Foroud T, McClintick JN, McGee BM, Yang AY, Siemieniak DR, Stark KR, Gruppo R, Sarode R, Shurin SB, Chandrasekaran V, Stabler SP, Sabio H, Bouhassira EE, Upshaw JD Jr, Ginsburg D, Tsai HM. <strong style="mso-bidi-font-weight: normal;">Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura. </strong></span><span style="mso-bidi-font-size: 11.0pt; mso-bidi-font-family: Arial;">Nature. 2001; 413(6855):488-94. PMID: 11586351. <u>Cited by 1683</u></span></p>
<p class="MsoListParagraph" style="margin-left: 31.5pt; text-indent: -.25in; mso-list: l2 level1 lfo4; mso-layout-grid-align: none; text-autospace: ideograph-numeric ideograph-other;"><!-- [if !supportLists]--><span style="mso-bidi-font-size: 11.0pt; mso-fareast-font-family: Arial; mso-bidi-font-family: Arial;"><span style="mso-list: Ignore;">2.<span style="font: 7.0pt 'Times New Roman';">&nbsp;&nbsp;&nbsp; </span></span></span><!--[endif]--><span style="mso-bidi-font-family: Arial;">Zhou W, Dong L, Ginsburg D, Bouhassira EE, Tsai HM. <strong style="mso-bidi-font-weight: normal;">Enzymatically active ADAMTS13 variants are not inhibited by anti-ADAMTS13 autoantibodies: a novel therapeutic strategy?</strong> </span><span style="mso-bidi-font-size: 11.0pt; mso-bidi-font-family: Arial;">The Journal of biological chemistry. 2005; 280(48):39934-41. PMID: 16203734</span><span style="mso-bidi-font-size: 11.0pt;"> <span style="mso-spacerun: yes;">&nbsp;&nbsp;</span></span><u><span style="mso-bidi-font-size: 11.0pt; mso-bidi-font-family: Arial;">Cited by 59</span></u><span style="mso-bidi-font-size: 11.0pt;"><span style="mso-spacerun: yes;">&nbsp;</span></span></p>
<p class="MsoListParagraph" style="margin-left: 31.5pt; text-indent: -.25in; mso-list: l2 level1 lfo4; mso-layout-grid-align: none; text-autospace: ideograph-numeric ideograph-other;"><!-- [if !supportLists]--><span style="mso-bidi-font-size: 11.0pt; mso-fareast-font-family: Arial; mso-bidi-font-family: Arial;"><span style="mso-list: Ignore;">3.<span style="font: 7.0pt 'Times New Roman';">&nbsp;&nbsp;&nbsp; </span></span></span><!--[endif]--><span style="mso-bidi-font-family: Arial;">Zhou W, Inada M, Lee TP, Benten D, Lyubsky S, Bouhassira EE, Gupta S, Tsai HM.<strong style="mso-bidi-font-weight: normal;"> ADAMTS13 is expressed in hepatic stellate cells. </strong>Laboratory investigation; </span><span style="mso-bidi-font-size: 11.0pt; mso-bidi-font-family: Arial;">a journal of technical methods and pathology. 2005; 85(6):780-8. PMID: 15806136<span style="mso-spacerun: yes;">&nbsp; </span><u>Cited by 162</u></span><span style="mso-bidi-font-size: 11.0pt;"><span style="mso-spacerun: yes;">&nbsp;</span></span></p>
<p class="MsoListParagraph" style="margin-left: 31.5pt; text-indent: -.25in; mso-list: l2 level1 lfo4; mso-layout-grid-align: none; text-autospace: ideograph-numeric ideograph-other;"><!-- [if !supportLists]--><span style="mso-bidi-font-size: 11.0pt; mso-fareast-font-family: Arial; mso-bidi-font-family: Arial;"><span style="mso-list: Ignore;">4.<span style="font: 7.0pt 'Times New Roman';">&nbsp;&nbsp;&nbsp; </span></span></span><!--[endif]--><span lang="FR" style="mso-bidi-font-family: Arial; mso-ansi-language: FR;">Zhou W, Bouhassira EE, Tsai HM. </span><strong style="mso-bidi-font-weight: normal;"><span style="mso-bidi-font-family: Arial;">An IAP retrotransposon in the mouse ADAMTS13 gene creates ADAMTS13 variant proteins that are less effective in cleaving von Willebrand factor multimers.</span></strong> <span style="mso-bidi-font-size: 11.0pt; mso-bidi-font-family: Arial;">Blood. 2007; 110(3):886-93. PMID: 17426255<span style="mso-spacerun: yes;">&nbsp;&nbsp; </span><u>Cited by 38</u></span></p>
<p class="MsoListParagraph" style="margin-left: 31.5pt; text-indent: -.25in; mso-list: l2 level1 lfo4; mso-layout-grid-align: none; text-autospace: ideograph-numeric ideograph-other;"><strong><span style="background: lightgrey;">Characterization of replication timing and replication origins in human primary erythroid cells</span></strong></p>
<p class="MsoNormal" style="text-align: justify; text-indent: 0.25in;">Gene transcription is regulated by transcription factors and by chromatin structure. Using the Recombinase-Mediated Cassette Exchange (RMCE) method and&nbsp;<span style="font-family: Symbol;">b</span>-globin transgenes as a model, we demonstrated that replication timing plays a critical role in gene expression at some genetic loci in erythroid cells. This prompted us to investigate the mechanisms that regulate replication timing in basophilic erythroblasts. In collaboration with the Schildkraut and Mieg labs, we developed the TimEX and TimEX-seq method to measure replication timing genome-wide using tiling micro-arrays and massively parallel sequencing. We applied these methods to generate genome-wide maps of replication timing in several cell types that demonstrated that replication timing is very tightly regulated in mammalian cells and that the timing of replication and gene expression levels are very closely linked.&nbsp;</p>
<p class="MsoNormal" style="margin-left: 4.5pt; text-align: justify; text-indent: 0.25in;">In collaboration with the Aladjem lab, we also developed methods to generate allele-specific profiles of replication timing and replication origins. Using these maps and a novel analytic approach, we show that the two chromosome homologs replicate within a few minutes of each other in about 92% of the genome but that about 8% of the genome replicate asynchronously. Asynchrony is associated with imprinting random mono-allelic expression and proximity to large structural variants. We also showed that an asymmetry in nucleotide distribution, which increases the propensity of origins to unwind and adopt non-B DNA structure, rather than the ability to form G4-quadruplexes, is directly associated with origin activity. This work also led to the development of GenPlay, a powerful, JAVA, open-source genome browser and analyzer application that is available online and currently utilized by over 100 labs worldwide.</p>
<p class="MsoListParagraph" style="margin-left: 0.25in; text-align: justify; text-indent: -0.25in;">1.<span style="font-variant-numeric: normal; font-variant-east-asian: normal; font-stretch: normal; font-size: 7pt; line-height: normal; font-family: 'Times New Roman';">&nbsp;&nbsp;&nbsp;&nbsp;</span>Fu H., Lixin W., Lin CH, Singhania S, Bouhassira EE, Aladjem MI.&nbsp;<strong>Human Replicators Can Prevent Gene Silencing</strong>.&nbsp;Nature Biotech.&nbsp;&nbsp;2006, 24(5):572-6. PMID: 16604060&nbsp;<u>Cited by 37</u>&nbsp;</p>
<p class="MsoListParagraph" style="margin-left: 0.25in; text-align: justify; text-indent: -0.25in;">2.<span style="font-variant-numeric: normal; font-variant-east-asian: normal; font-stretch: normal; font-size: 7pt; line-height: normal; font-family: 'Times New Roman';">&nbsp;&nbsp;&nbsp;&nbsp;</span>Desprat R, Thierry-Mieg D, Lailler N, Lajugie J, Schildkraut C, Thierry-Mieg J, Bouhassira EE.&nbsp;<strong>Predictable dynamic program of timing of DNA replication in human cells.</strong>&nbsp;Genome Research. 2009 Dec;19(12):2288-99. PMID: 19767418&nbsp;<u>Cited by 117</u></p>
<p class="MsoListParagraph"><span style="text-align: justify; text-indent: -0.25in;">3.<span style="font-variant-numeric: normal; font-variant-east-asian: normal; font-stretch: normal; font-size: 7pt; line-height: normal; font-family: 'Times New Roman';">&nbsp;&nbsp;&nbsp;&nbsp;</span></span><span style="text-align: justify; text-indent: -0.25in;">Mukhopadhyay R, Lajugie J, Fourel&nbsp;&nbsp;N, Selzer A, Schizas M, Bartholdy B, Mar&nbsp;&nbsp;J, Lin&nbsp;&nbsp;CM, Martin MM , Ryan&nbsp;&nbsp;M, Aladjem MI and Bouhassira EE.&nbsp;<strong>Allele-Specific Genome-wide Profiling in Human Primary Erythroblasts Reveal Replication Program Organization.&nbsp;</strong></span><span style="text-align: justify; text-indent: -0.25in;">PLoS Genet. 2014 May 1;10(5):e1004319.&nbsp;&nbsp;PMID: 24787348&nbsp;&nbsp;<u>Cited by 42</u></span>&nbsp;</p>
<p class="MsoListParagraph" style="margin-left: 0.25in; text-align: justify; text-indent: -0.25in;">4.<span style="font-variant-numeric: normal; font-variant-east-asian: normal; font-stretch: normal; font-size: 7pt; line-height: normal; font-family: 'Times New Roman';">&nbsp;&nbsp;&nbsp;&nbsp;</span>Bartholdy B, Mukhopadhyay R, Lajugie J, Aladjem MI, Bouhassira EE.&nbsp;<strong>Allele-specific analysis of DNA replication origins in mammalian cells.</strong>&nbsp;Nat Commun. 2015 May 19;6:7051.&nbsp;PMID: 25987481&nbsp;<u>Cited by 32</u></p>

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Sanjeev Gupta

Submitted by Anonymous (not verified) on
Full Name
Sanjeev Gupta
Profile Image URL
https://documentapi-fargate-documentbucket-15qi4tpdvnhlz.s3.amazonaws.com/218/320e3550-5d55-11ef-82d4-99c0ef58f445.jpg
Type
Provider
Faculty
Expert
First Name
Sanjeev
Last Name
Gupta
NPI
1831274315
Faculty ID
8041
Employment Status
Full Time
Patient Type
Adult
Department
einstein-dept-medicine
einstein-dept-pathology
Gender
Male
Email
sanjeev.gupta@einsteinmed.edu
Phone
718-430-3309
Titles
Type
Academic
Department
Department of Medicine
Department Link
Rank
Professor
Division
Hepatology
Type
Academic
Department
Department of Pathology
Department Link
Rank
Professor
Type
Administrative
Title
The Eleazar & Feige Reicher Chair in Translational Medicine, Department of Medicine
Tags
me-patientcare-cancer-research-stem-cell-cancer-biology
Locations
Is Primary
On
Type
Clinical
Location (Address, State, City, Zip)
Not used, will be deleted
Coordinates
POINT (-73.84154 40.84612)
Address Line 1
1250 Waters place
City
Bronx
State
NY
Zip
10461-2720
Location Title
Montefiore at 1250 Waters Place
Is Primary
Off
Type
Academic
Location (Address, State, City, Zip)
Not used, will be deleted
Coordinates
POINT (-73.8459022 40.8504961)
Building
Ullmann Building
Room
625
Address Line 1
Albert Einstein College of Medicine
Address Line 2
Jack and Pearl Resnick Campus
Address Line 3
1300 Morris Park Avenue
City
Bronx
State
NY
Zip
10461
Location Title
Albert Einstein College of Medicine
Education and Trainings
Education Type Label
Medical Education
Education Institution
University of Rajasthan, Sardar Patel Med Coll
Education Type Label
Fellowship
Education Institution
Hammersmith Hospital
Education Type Label
Fellowship
Education Institution
Los Angeles County and Univ of Southern CA
Education Type Label
Fellowship
Education Institution
Jacobi Medical Center
Education Type Label
Residency
Education Institution
Jacobi Medical Center
Education Type Label
Residency
Education Institution
Postgraduate Institute of Medical Educ. & Research
Education Type Label
Residency
Education Institution
Hammersmith Hospital
Professional Interests

<p>Liver regeneration is critical for health. We focus on physiology of liver regeneration during development, early childhood and adulthood to inform mechanistic disruptions in diseases. The latter ranges from acute liver failure, effects of drugs, toxins, alcohol, virus hepatitis, obesity-related metabolic (or nonalcoholic) liver disease, chronic hepatitis, e.g., Wilson disease with copper toxicosis, and allograft rejection. The mechanisms concerning DNA damage response directed by ATM gene and downstream partners are of considerable interest to us.&nbsp; &nbsp; &nbsp;</p>
<p>These aspects are joined with study of cell type-specific contributions as well as aspects of stem cell biology for liver regeneration. We apply cell transplantation approaches to better understand the biology and regenerative potential of various cell types. Expression of therapeutic constructs and transplantation of those cells is another area of investigative interest. We address the role of endogenous stem/progenitor cells in therapeutic development. Tissue engineering to generate auxiliary liver has potential in these areas and is also advancing liver regenerartion in experimental models.</p>
<p>We use a variety of methods, including microarrays or deep sequencing for gene expression, cell and molecular biology methods, and multiple small and large animal models. The findings are integrated with analyses of human tissue and blood samples.</p>
<p>Unique aspects of our work include use of established drugs for mechanistic interrogations and therapeutic applications, and an uncommon depth and breadth of multidisciplinary tools. We collaborate with leading investigators at Einstein or elsewhere as appropriate.</p>

Research Areas
Liver regeneration in health and disease
Biology and differentiation of hepatic stem cells
DNA damage response involving ATM and downstream pathways
Translational studies using liver cell and animal models
Therapeutics including cell and gene therapy
Areas of Expertise
Stem cell research
Expert Summary

<p class="MsoNormal" style="line-height: 15.6pt;"><span style="font-size: 9.0pt;">Dr. Gupta is a pioneer in the development of cell therapy &ndash; treating disease by introducing healthy cells into the body.&nbsp; He has discovered various mechanisms for coaxing transplanted cells to attach to host tissue and multiply, paving the way for treating health problems such as&nbsp; high cholesterol, hemophilia, liver failure, and hepatitis.&nbsp;</span></p>
<p class="MsoNormal" style="line-height: 15.6pt;"><span style="font-size: 9.0pt;">Dr. Gupta has successfully manipulated human stem cells to generate liver cells and defined some of the fundamental ways by which gene expression is regulated in stem cells. Dr. Gupta serves as an expert for the National Institutes of Health, U.S. Department of Veterans Affairs, U.S. Department of Defense, Wellcome Trust, and national scientific bodies in over ten countries.</span></p>
<p class="MsoNormal" style="line-height: 15.6pt;"><span style="font-size: 9.0pt;">In the 1990s, Dr. Gupta contributed to the first ever clinical trial of a cell/gene therapy for familial hypercholesterolemia (high cholesterol), which results from a gene defect. He also showed that Wilson&rsquo;s disease (a genetic condition characterized by excessive accumulation of copper in the liver and brain) could potentially be cured by use of cell therapy.&nbsp;</span></p>

CHAM Provider
Off
Professional Title
M.B.,B.S.
M.D.
Selected Publications

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<ul type="disc">
<li>Thirunavukkarasu C, Sharma Y, Tchaikovskaya T, Maslov AY, Gupta S. Transcriptional profiling reveals ataxia telangiectasia mutated pathways regulate joint copper and arsenic toxicity for hepatic metalloplasia and anti-cancer therapies. Life Sci. 2022 Jul 6;120787. doi: 10.1016/j.lfs.2022.120787.&nbsp;</li>
<li>Chang CJ, Ge EJ Bush AI, Casini A, Cobine PA, Cross JR, DeNicola GM, Dou Q, Franz KJ, Gohil VM, Gupta S, Kaler SG, Lutsenko S, Mittal V, Petris MJ, Polishchuk R, Ralle M, Schilsky ML, Tonks NK, Vahdat LK, Van Aelst L, Xi D, Yuan P, Brady DC. Connecting copper and cancer from transition metal signaling to metalloplasia in the clinic. Nat Rev Cancer 2022 Feb;22(2):102-113. doi: 10.1038/s41568-021-00417-2. Epub 2021 Nov 11. PMID: 34764459</li>
<li>Viswanathan P, Gupta P, Sharma Y, Maisuradze L, Bandi S, Gupta S. Caffeine disrupts ataxia telangiectasia mutated gene-related pathways and exacerbates acetaminophen toxicity in human fetal immortalized hepatocytes. Toxicology. 2021 May 7;457:152811. doi: 10.1016/j.tox.2021.152811. PMID: 33971260</li>
<li>Viswanathan P, Sharma Y, Jaber FL, Tchaikovskaya T, Gupta S. Transplanted hepatocytes rescue mice in acetaminophen-induced acute liver failure through paracrine signals for hepatic ATM and STAT3 pathways. FASEB J 2021 Apr;35(4):e21471. doi: 10.1096/fj.202002421R. PMID: 33683737</li>
<li>Jaber FL, Sharma Y, Mui BG, Kapoor S, Gupta S. Tumor necrosis factor directs allograft-related innate responses and its neutralization improves hepatocyte engraftment in rats. Am J Pathol 2021; 191(1):79-89. doi: 10.1016/j.ajpath.2020.09.014. Epub 2020 Oct 27. PMID: 33127336</li>
<li>Viswanathan P, Sharma Y, Gupta S. Ataxia telangiectasia mutated pathway disruption affects hepatic DNA and tissue damage in nonalcoholic fatty liver disease. Exp Mol Pathol. 2020 Apr; 113:104369. doi: 10.1016/j.yexmp.2020.104369. Epub 2020 Jan 7. PMID: 31917286</li>
<li>Gupta P, Sharma Y, Viswanathan P, Gupta S. Cellular receptor signaling and ATM pathway intersections regulate hepatic DNA repair. Cytokine 2020 Mar; 127:154946. doi: 10.1016/j.cyto.2019.154946. Epub 2019 Dec 11. PMID: 31837586</li>
<li>Bandi S, Tchaikovskaya T, Gupta S. Hepatic differentiation in human pluripotent stem cells by developmental stage-specific metabolomics products. Differentiation 2019; 105:54-70. Jan 28;105:54-70. doi: 10.1016/j.diff.2019.01.005. PMID: 30776728.</li>
<li>Kakabadze Z, Karalashvili L, Chakhunashvili D, Havlioglu N, Janelidze M, Kakabadze A, Sharma Y, Gupta S. Decellularized bovine placentome for portacavally-interposed heterotopic liver transplantation in rats. Mater Sci Eng C Mater Biol Appl. 2019 Apr; 97:293-301. doi: 10.1016/j.msec.2018.12.025. Epub 2018 Dec 10. PMID: 30678914.</li>
<li>Yadav N, Jaber FL, Sharma Y, Viswanathan P, Gupta S. Efficient reconstitution of hepatic microvasculature by endothelin receptor antagonism in liver sinusoidal endothelial cells. Hum Gene Ther 2018; Sep 28. doi: 10.1089/hum.2018.166. PMID: 30266073,&nbsp;</li>
<li>Sharma Y, Liu J, Kristian KE, Follenzi A, Gupta S. In Atp7b-/- mice modeling Wilson's disease liver repopulation with bone marrow-derived myofibroblasts or inflammatory cells and not hepatocytes is delterious.&nbsp;<span title="Gene expression">Gene Expr</span>. 2018 Jul 20. doi: 10.3727/105221618X15320123457380. PMID: 30029699</li>
<li>Bandi S, Gupta S, Tchaikovskaya T, Gupta S. Differentiation in stem/progenitor cells along fetal or adult hepatic stages requires transcriptional regulators independently of oscillations in microRNA expression.&nbsp;<span title="Experimental cell research">Exp Cell Res</span>. 2018 Sep 1;370(1):1-12. doi: 10.1016/j.yexcr.2018.06.004. Epub 2018 Jun 6.</li>
<li>Benten D, Kluwe J, Wirth JW, Thiele ND, Follenzi A, Bhargava KK, Palestro CJ, Koepke M, Tjandra R, Volz T, Lutgehetmann M, Gupta S. A humanized mouse model with liver fibrosis following expansion of transplanted hepatic stellate cells in injury and inflammation. Lab Invest 2018 Apr;98(4):525-536. doi: 10.1038/s41374-017-0010-7. Epub 2018 Jan 19.PMID: 29352225.</li>
<li>Viswanathan P, Sharma Y, Gupta P, Gupta S. Replicative stress and alterations in cell cycle checkpoint controls following acetaminophen hepatotoxicity restrict hepatic regeneration. Cell Prolif 2018; Jun;51(3):e12445. doi: 10.1111/cpr.12445. Epub 2018 Mar 5. PMID: 29504225.</li>
<li>Kakabadze Z, Kakabadze A, Chakhunashvili D, Karalashvili L, Berishvili E, Sharma Y, Gupta S. Decellularized human placenta supports hepatic tissue and allows rescue in acute liver failure. Hepatology 2018 May;67(5):1956-1969.&nbsp;PMID: 29211918.&nbsp;</li>
</ul>

EMR ID
3601
Is Open Scheduling
Off

Chandan Guha

Submitted by Anonymous (not verified) on
Full Name
Chandan Guha
Profile Image URL
https://assets.montefioreeinstein.org/profiles/images/physphoto/Guha_Chandan_MD_420x504.jpg
Type
Provider
Faculty
Expert
First Name
Chandan
Last Name
Guha
NPI
1093917924
Faculty ID
7020
Employment Status
Full Time
Patient Type
Adult
Department
einstein-dept-radiation-oncology
einstein-dept-pathology
einstein-dept-urology
Gender
Male
Email
cguha@montefiore.org
Phone
718-920-2702
Titles
Type
Academic
Department
Department of Radiation Oncology
Rank
Professor
Type
Academic
Department
Department of Pathology
Department Link
Rank
Professor
Type
Academic
Department
Department of Urology
Department Link
Rank
Professor
Type
Clinical
Title
Associate Director for Clinical/Translational Research, Institute for Immunotherapy
Tags
me-patientcare-cancer-research-immunotherapy
Type
Administrative
Title
Associate Director, Innovation/Tech Transfer, Montefiore Einstein Comprehensive Cancer Center
Tags
me-patientcare-cancer-about-associate-directors
me-patientcare-cancer-research-therapeutics
Type
Administrative
Title
Vice Chair, Department of Radiation Oncology
Tags
me-patientcare-cancer-clinical-gastrointestinal
me-patientcare-cancer-clinical-genitourinary-urologic
Type
Administrative
Title
The Harry Eagle Chair in Cancer Research/National Women's Division
Locations
Is Primary
On
Type
Clinical
Location (Address, State, City, Zip)
Not used, will be deleted
Coordinates
POINT (-73.84599 40.84617)
Address Line 1
1625 Poplar Street
City
Bronx
State
NY
Zip
10462-2653
Location Title
Montefiore Medical Park at 1625 Poplar
Is Primary
Off
Type
Academic
Location (Address, State, City, Zip)
Not used, will be deleted
Coordinates
POINT (-73.8459022 40.8504961)
Building
Block
Room
620
Address Line 1
Albert Einstein College of Medicine
Address Line 2
Jack and Pearl Resnick Campus
Address Line 3
1300 Morris Park Avenue
City
Bronx
State
NY
Zip
10461
Location Title
Albert Einstein College of Medicine
Education and Trainings
Education Type Label
Medical Education
Education Institution
Calcutta University
Education Type Label
Residency
Education Institution
Montefiore Medical Center
Education Type Label
Residency
Education Institution
Washington University School of Medicine
Professional Interests

<p><strong>Exploring therapeutic potential of stem cell regeneration in the event of radiation insult </strong><br />Exposure to high doses of ionizing radiation in the event of therapeutic, accidental or intentional incident such as nuclear/radiological warfare can lead to debilitating injuries to multiple organs resulting in death within days depending on the amount of radiation dose and the quality of radiation. Unfortunately, there is not a single FDA-licensed drug approved against acute radiation injury.</p>
<p>Radiation damage to multiple organs often described as multiple organ dysfunction syndrome (MODS) or acute radiation syndrome (ARS) results from rapid depletion of radiosensitive cells, these cells are usually the stem or progenitor cells with high proliferative capacity; naturally, bone marrow stem cells (BMSC), and intestinal stem cells (ISC), which are extremely critical in maintaining a pool of peripheral blood cells and in maintaining villi for the absorption of nutrients are highly sensitive to radiation. One of the most efficient ways of rescuing MODS is to administer fresh cells that can repair, support and/or replace the damaged cells and repopulate the damaged tissue with healthy cells. The Rad-Stem Center for Medical Countermeasures against Radiation (RadStem CMCR) program at Einstein is developing stem cell-based therapies to treat acute radiation syndrome (ARS) that results from radiation injury.</p>
<p>Radiation-induced gastrointestinal syndrome (RIGS) results from a combination of direct damage to intestinal crypt and endothelial cells, and subsequent loss of the mucosal barrier leading to microbial infection, septic shock and systemic inflammatory response syndrome (SIRS). Currently, there is no treatment for RIGS in clinic. Irradiation induces apoptosis of crypt ISC, endothelial cells and enterocytes within hours. Acute loss of cells in situ requires rapid compensation of their functions and this is best achieved using cell replacement therapies. We are interested in exploring intestinal regenerative therapy with a combination of systemic administration of growth factors and cell replacement therapy to salvage Gl function post-radiation exposure. We are testing combinations of: a) intestinal stem cell growth factor, R-spondinl (R-spol), b) TLR ligands, and c) transplantation of bone marrow-derived endothelial progenitor cells (EPC) and mesenchymal stem cells (MSC) to restore IR-damaged ISC niche, protect against IR-induced cell death and provide growth signals for host ISC regeneration, thus providing protection and mitigation from RIGS.</p>
<p><strong>Preparative live irradiation for hepatocyte transplant in acute liver injury and cirrhosis </strong><br />Hepatocyte transplantation (HT) is a very attractive alternative to liver transplant in the treatment of both inherited and acquired liver diseases. However, benefits of this procedure are currently limited by the inability of the transplanted hepatocytes to proliferate in the host liver, and lack of a noninvasive method to evaluate the repopulation of transplanted hepatocytes in the liver. In order to develop a clinically feasible protocol for HT, we are exploring preparative hepatic irradiation (HIR) for liver repopulation (in place of liver transplant) to deplete host hepatocytes and permit preferential proliferation of the engrafted donor cells in response to hepatic mitotic stimuli.<strong> &nbsp;</strong>Our lab was the first one to demonstrate that preparative HIR and partial hepatectomy (PH), followed by HT results in the replacement of virtually all host hepatocytes by the transplanted non-irradiated hepatocytes in 12 weeks. We are interested in using inducible pluripotent stem cells (iPSC)- derived hepatocytes following highly focused irradiation of the damaged liver in place of a liver transplant. We are also interested in exploring non-invasive biomarkers to validate that the transplanted hepatocytes can efficiently replace host hepatocytes upon liver irradiation.</p>
<p><strong>Cancer Immunotherapy </strong><br />Radiation therapy (RT) has been used as a standard treatment modality for many solid tumors. While tumoricidal properties of RT are instrumental for standard clinical application, irradiated tumors can potentially serve as a source of tumor antigens <em>in vivo</em>, where dying tumor cells would release various tumor antigens slowly over time. Using different<em> in vitro</em> and <em>in vivo</em> tumor models we, and others, demonstrated that RT enhances oxidative stress, and augments the release of necessary activating signals for DC such as endogenous danger associated molecular pattern (DAMP) molecules from irradiated cells. These RT-mediated processes lead to an increase antigenecity of irradiated cells which augments antigen presentation leading to an effective anti-tumoral immune responses. However the underlying mechanism of this processes has still to be determined.</p>
<p>Over the last years we have been interested in designing novel tumor vaccines that amplify the tumor immune response using conventional and exploratory cancer therapies. In particular we are focusing on evaluating the immunogenic properties of radiation therapies and determine how immunotherapeutic molecules can synergize with RT in boosting immune cells cell function. We are also interested in exploring therapeutic effect of ultrasound therapy in the treatment of solid tumor. Our recent work on use of Listeria-based vaccine therapy in combination of RT shows that this strategy is more effective than RT alone.</p>

Specialties
Areas of Expertise
Targeted delivery of chemotherapy and immunotherapies for cancer
Cancer radiation treatment dosage and standards
Expert Summary

<p>Dr. Guha is a radiation oncologist who specializes in prostate, genitourinary, liver and GI malignancies, and radio surgery. His research interests include development of stem-cell based therapies to treat radiation-induced toxicity and prevent death in patients.</p>

CHAM Provider
Off
Professional Title
M.B.,B.S.
Ph.D.
Selected Publications

<p><strong>Immunomodulation of radiation therapy: Radiation-enhanced tumor vaccines</strong></p>
<ol>
<li>Ahmed MM, Guha C, Hodge JW, Jaffee E. Immunobiology of Radiotherapy: New Paradigms. Radiat Res. 2014, Aug;182(2):123-5</li>
<li>Almo SC, Guha C. Considerations for Combined Immune Checkpoint Modulation and Radiation Treatment. Radiat Res. 2014, Aug;182(2):230-8</li>
<li>Kawashita Y, Deb NJ, Garg M, Kabarriti R, Alfieri A, Takahashi M, Roy-Chowdhury J, Guha C. An Autologous In Situ Tumor Vaccination Approach for Hepatocellular Carcinoma. Flt3 Ligand Gene Transfer Increases Antitumor Effects of a Radio-Inducible Suicide Gene Therapy in an Ectopic Tumor Model. Radiat Res. 2014 Aug;182(2):201-10</li>
<li>Bernstein, Michael B; Garnett, Charlie T; Zhang, Huogang; Velcich, Anna; Wattenberg, Max M; Gameiro, Sofia R; Kalnicki, Shalom; Hodge, James W; Guha, Chandan. Radiation-induced modulation of costimulatory and coinhibitory T-cell signaling molecules on human prostate carcinoma cells promotes productive antitumor immune interactions. Cancer biotherapy &amp; radiopharmaceuticals, 2014 May; 29 (4):153-61</li>
<li>Ahmed MM, Hodge JW, Guha C, Bernhard EJ, Vikram B, Coleman CN. Harnessing the potential of radiation-induced immune modulation for cancer therapy. Cancer Immunol Res. 2013 Nov;1(5):280-4</li>
<li>Gameiro SR, Higgins JP, Dreher MR, Woods DL, Reddy G, Wood BJ, Guha C, Hodge JW. Combination therapy with local radiofrequency ablation and systemic vaccine enhances antitumor immunity and mediates local and distal tumor regression. PLoS One. 2013 Jul 24;8(7)</li>
<li>Zhang, Huagang; Liu, Laibin; Yu, Dong; Kandimalla, Ekambar R; Sun, Hui Bin; Agrawal, Sudhir; Guha, Chandan. An in situ autologous tumor vaccination with combined radiation therapy and TLR9 agonist therapy. PloS one, 2012; 7 (5)</li>
<li>Hannan, Raquibul; Zhang, Huagang; Wallecha, Anu; Singh, Reshma; Liu, Laibin; Cohen, Patrice; Alfieri, Alan; Rothman, John; Guha, Chandan. Combined immunotherapy with Listeria monocytogenes-based PSA vaccine and radiation therapy leads to a therapeutic response in a murine model of prostate cancer. Cancer immunology, immunotherapy: CII, 2012 Dec; 61 (12):2227-38</li>
</ol>
<p><strong>Stem cell based therapy for radiation injury</strong></p>
<ol>
<li>Benderitter, Marc; Caviggioli, Fabio; Chapel, Alain; Coppes, Robert P; Guha, Chandan; Klinger, Marco; Malard, Olivier; Stewart, Fiona; Tamarat, Radia; Luijk, Peter Van; Limoli, Charles L. Stem Cell Therapies for the Treatment of Radiation-Induced Normal Tissue Side Effects. Antioxidants &amp; redox signaling, 2014, Jul 10;21(2):338-55</li>
<li>Zachman, Derek K; Leon, Ronald P; Das, Prerna; Goldman, Devorah C; Hamlin, Kimberly L; Guha, Chandan; Fleming, William H. Endothelial cells mitigate DNA damage and promote the regeneration of hematopoietic stem cells after radiation injury. Stem cell research, 2013 Nov; 11 (3):1013-21</li>
<li>Saha, Subhrajit; Bhanja, Payel; Liu, Laibin; Alfieri, Alan A; Yu, Dong; Kandimalla, Ekambar R; Agrawal, Sudhir; Guha, Chandan, &lsquo;TLR9 agonist protects mice from radiation-induced gastrointestinal syndrome&rsquo;; PloS one, 2012; 7 (1)</li>
<li>Saha, Subhrajit; Bhanja, Payel; Kabarriti, Rafi; Liu, Laibin; Alfieri, Alan A; Guha, Chandan,. Bone marrow stromal cell transplantation mitigates radiation-induced gastrointestinal syndrome in mice. PloS one, 2011; 6 (9)</li>
<li>Bhanja P, Saha S, Kabarriti R, Liu L, Roy-Chowdhury N, Roy-Chowdhury J, Sellers RS, Alfieri AA, Guha C. Protective role of R-spondin1, an intestinal stem cell growth factor, against radiation-induced gastrointestinal syndrome in mice. PLoS One. 2009 Nov 24;4(11)</li>
</ol>
<p><strong>Preparative irradiation to facilitate liver cell repopulation and stem cell engraftment <em>in vivo</em></strong></p>
<ol>
<li>Vainshtein, Jeffrey M; Kabarriti, Rafi; Mehta, Keyur J; Roy-Chowdhury, Jayanta; Guha, Chandan. Bone Marrow-Derived Stromal Cell Therapy in Cirrhosis: Clinical Evidence, Cellular Mechanisms, and Implications for the Treatment of Hepatocellular Carcinoma. International journal of radiation oncology, biology, physics, 2014 Jul 15; 89 (4):786-803</li>
<li>Vainshtein, Jeffrey M; Kabarriti, Rafi; Mehta, Keyur J; Roy-Chowdhury, Jayanta; Guha, Chandan. Bone Marrow-Derived Stromal Cell Therapy in Cirrhosis: Clinical Evidence, Cellular Mechanisms, and Implications for the Treatment of Hepatocellular Carcinoma. International journal of radiation oncology, biology, physics. 2014 Jul 15; 89 (4):786-803</li>
<li>Yannam, Govardhana Rao; Han, Bing; Setoyama, Kentaro; Yamamoto, Toshiyuki; Ito, Ryotaro; Brooks, Jenna M; Guzman-Lepe, Jorge; Galambos, Csaba; Fong, Jason V; Deutsch, Melvin; Quader, Mubina A; Yamanouchi, Kosho; Kabarriti, Rafi; Mehta, Keyur; Soto-Gutierrez, Alejandro; Roy-Chowdhury, Jayanta; Locker, Joseph; Abe, Michio; Enke, Charles A; Baranowska-Kortylewicz, Janina; Solberg, Timothy D; Guha, Chandan; Fox, Ira J. A nonhuman primate model of human radiation-induced venocclusive liver disease and hepatocyte injury. International journal of radiation oncology, biology, physics, 2014 Feb 1; 88 (2):404-11</li>
<li>Miyazaki, Kensuke; Yamanouchi, Kosho; Sakai, Yusuke; Yamaguchi, Izumi; Takatsuki, Mitsuhisa; Kuroki, Tamotsu; Guha, Chandan; Eguchi, Susumu, &lsquo;Construction of liver tissue in&yacute;&yacute;vivo with preparative partial hepatic irradiation and growth stimulus: investigations of less invasive techniques and progenitor cells&rsquo;; The Journal of surgical research. 2013 Dec; 185 (2):889-95</li>
<li>Puppi, Juliana; Strom, Stephen C; Hughes, Robin D; Bansal, Sanjay; Castell, Jose V; Dagher, Ibrahim; Ellis, Ewa C S; Nowak, Greg; Ericzon, Bo-Goran; Fox, Ira J; Gomez-Lechon, M Jose; Guha, Chandan; Gupta, Sanjeev; Mitry, Ragai R; Ohashi, Kazuo; Ott, Michael; Reid, Lola M; Roy-Chowdhury, Jayanta; Sokal, Etienne; Weber, Anne; Dhawan, Anil, &lsquo;Improving the techniques for human hepatocyte transplantation: report from a consensus meeting in London&rsquo;; Cell transplantation. 2012; 21 (1):1-10</li>
<li>Zhou, Hongchao; Dong, Xinyuan; Kabarriti, Rafi; Chen, Yong; Avsar, Yesim; Wang, Xia; Ding, Jianqiang; Liu, Laibin; Fox, Ira J; Roy-Chowdhury, Jayanta; Roy-Chowdhury, Namita; Guha, Chandan. Single liver lobe repopulation with wildtype hepatocytes using regional hepatic irradiation cures jaundice in Gunn rats. PloS one. 2012; 7 (10)</li>
<li>Ding, Jianqiang; Yannam, Govardhana R; Roy-Chowdhury, Namita; Hidvegi, Tunda; Basma, Hesham; Rennard, Stephen I; Wong, Ronald J; Avsar, Yesim; Guha, Chandan; Perlmutter, David H; Fox, Ira J; Roy-Chowdhury, Jayanta. Spontaneous hepatic repopulation in transgenic mice expressing mutant human &yacute;&yacute;1-antitrypsin by wild-type donor hepatocytes. The Journal of clinical investigation, 2011 May; 121 (5):1930-4</li>
<li>Soltys, Kyle A; Soto-Gutierrez, Alejandro; Nagaya, Masaki; Baskin, Kevin M; Deutsch, Melvin; Ito, Ryotaro; Shneider, Benjamin L; Squires, Robert; Vockley, Jerry; Guha, Chandan; Roy-Chowdhury, Jayanta; Strom, Stephen C; Platt, Jeffrey L; Fox, Ira J. Barriers to the successful treatment of liver disease by hepatocyte transplantation. Journal of hepatology, 2010 Oct; 53 (4):769-74</li>
<li>Dawson, Laura A; Guha, Chandan. Hepatocellular carcinoma: radiation therapy. Cancer journal (Sudbury, Mass.), 2008 Mar-Apr; 14 (2):111-6</li>
<li>Agoni, Lorenzo; Basu, Indranil; Gupta, Seema; Alfieri, Alan; Gambino, Angela; Goldberg, Gary L; Reddy, E Premkumar; Guha, Chandan. Rigosertib is a more effective radiosensitizer than cisplatin in concurrent chemoradiation treatment of cervical carcinoma, in vitro and in vivo. International journal of radiation oncology, biology, physics, 2014 Apr 1; 88 (5):1180-7</li>
</ol>

EMR ID
4049
Is Open Scheduling
Off

Roy S. Chuck

Submitted by Anonymous (not verified) on
Full Name
Roy S. Chuck
Profile Image URL
https://documentapi-fargate-documentbucket-15qi4tpdvnhlz.s3.amazonaws.com/218/99124b00-b3a6-11ee-8ab8-012a307002d3.jpg
Type
Provider
Faculty
Expert
First Name
Roy
Last Name
Chuck
NPI
1447202338
Faculty ID
11721
CMO Specialties
Clinical Terms
Employment Status
Full Time
Patient Type
Adult
Department
einstein-dept-ophthalmology-visual-sciences
einstein-dept-genetics
Gender
Male
Email
rchuck@montefiore.org
Phone
718-920-2020
Titles
Type
Academic
Department
Department of Ophthalmology & Visual Sciences
Department Link
Rank
Professor
Type
Academic
Department
Department of Genetics
Department Link
Rank
Professor
Type
Clinical
Title
Chairman, Department of Ophthalmology & Visual Sciences
Type
Clinical
Title
Professor and Chairman, Paul Henkind Chair, Department of Ophthalmology and Visual Sciences, Albert Einstein College of Medicine and Montefiore
Type
Administrative
Title
Chair, Department of Ophthalmology & Visual Sciences
Type
Administrative
Title
Paul Henkind Chair in Ophthalmology, Department of Ophthalmology & Visual Sciences
Locations
Is Primary
On
Type
Clinical
Location (Address, State, City, Zip)
Not used, will be deleted
Coordinates
POINT (-73.87862 40.88032)
Address Line 1
3400 Bainbridge Avenue
City
Bronx
State
NY
Zip
10467-240
Location Title
Montefiore Greene Medical Arts Pavilion
Is Primary
Off
Type
Clinical
Location (Address, State, City, Zip)
Not used, will be deleted
Coordinates
POINT (-73.85147 40.94383)
Address Line 1
1010 Central Park Avenue
City
Yonkers
State
NY
Zip
10704-1044
Location Title
Montefiore Medical Group-Cross County
Is Primary
Off
Type
Clinical
Location (Address, State, City, Zip)
Not used, will be deleted
Coordinates
POINT (-73.87526 40.8725)
Address Line 1
3170 Webster Avenue
City
Bronx
State
NY
Zip
10467
Location Title
Empire State Ambulatory Surgery Center
Is Primary
Off
Type
Academic
Location (Address, State, City, Zip)
Not used, will be deleted
Coordinates
POINT (-73.8785732 40.879979)
Address Line 1
Montefiore Medical Center
Address Line 2
Medical Arts Pavilion
Address Line 3
3400 Bainbridge Avenue
City
Bronx
State
NY
Zip
10467
Location Title
Montefiore Medical Center
Education and Trainings
Education Type Label
Medical Education
Education Institution
Columbia Univ College of Physicians and Surgeons
Education Type Label
Fellowship
Education Institution
University of Southern California Medical Center
Education Type Label
Residency
Education Institution
Washington University School of Medicine
Professional Interests

<p class="bodycopy">Dr. Roy S. Chuck is an ophthalmologist, visual scientist and geneticist known for his stem cell and dry eye research, and work in corneal restoration. He chairs Einstein&rsquo;s department of ophthalmology and visual sciences, one of only a handful of Asian-Americans to hold such a post in the U.S.</p>
<p class="bodycopy">&nbsp;</p>
<p class="bodycopy">He also chairs the ophthalmology department at Montefiore Medical Center, overseeing tertiary care to adult and pediatric patients with diseases of the eye, with subspecialty expertise that includes neuro-ophthalmology, plastic surgery, and retina, cornea and glaucoma services. The department maintains a program of ongoing community outreach aimed at early detection and treatment of eye diseases.</p>
<p class="bodycopy">&nbsp;</p>
<p class="bodycopy">Dr. Chuck is a cornea specialist with expertise in laser techniques for refractive eye conditions. He has deep research experience and holds multiple patents. His two main areas of research are corneal stem cell surgery and dry eye, the most common global eye disease. Recently, Dr. Chuck's team developed a unique mouse model of dry eye that allows animal testing of therapies. The model employs the use of <em>botulinum</em> toxin, commonly known as "botox," to block neurotransmitters in the tear-producing lacrimal gland. The resulting dry eye closely mimics that found in humans.</p>
<p class="bodycopy">&nbsp;</p>
<p class="bodycopy">Dr. Chuck is a long-time stem cell investigator in connection with corneal transplantation and sight restoration. His work includes cutting-edge corneal stem cell surgery, which has a success rate of nearly 50-percent&mdash;one of the highest for stem cell surgery.&nbsp; The operation is performed if the stem cell pool on the eye is wiped out through injury or a genetic condition. Without these regenerating cells, eye injuries, however small, result in opaque scars that reduce or even eliminate vision. Corneal stem cell surgery requires removing the scar tissue and transplanting donated corneal stem cells onto the eye. If successful, the introduced stem cells heal the wound and vision is restored.</p>
<p class="bodycopy">&nbsp;</p>
<p class="bodycopy">At Einstein, Dr. Chuck is developing research centers focusing on ophthalmologic disorders including cataracts, ocular surface disease/dry eye, glaucoma, macular degeneration, and eye conditions associated with diabetes.</p>

Research Areas
corneal spectroscopy
surgical device development
clinical trials
Areas of Expertise
Corneal disorders
Glaucoma
Refractive surgery
Stem Cell Research
Expert Summary

<div>Dr. Chuck is a prominent stem cell and dry eye researcher. He is a cornea specialist with expertise in the field of laser techniques, including LASIK surgery, corneal replacement, stem cell surgery, and refractive eye problems.&nbsp;</div>
<div><br />A basic scientist as well as a clinical researcher, Dr. Chuck has helped develop a unique model of dry eye using Botox that allows for testing of preclinical therapies. He has served as principal investigator on five FDA studies of vision correction and written more than 175 peer-reviewed papers and more than 100 book chapters and abstracts. Dr. Chuck has been featured several times on ABC News and ABC&rsquo;s &ldquo;Good Morning America&rdquo; on various eye diseases and conditions. He serves on the editorial boards of several publications, including the <em>Journal of Refractive Surgery</em> and <em>Lasers in Surgery and Medicine</em>.&nbsp;</div>

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Professional Title
M.D.
Ph.D.
Clinical Focus

Refractive surgery and corneal disorders including dry eye

Research Focus

Corneal reconstruction and stem cell surgery, dry eye, refractive surgery

EMR ID
5233
Biography

<p>Roy S. Chuck, MD, PhD, is Chairman and Professor, Ophthalmology &amp; Visual Sciences at Montefiore Einstein. Dr. Chuck&rsquo;s clinical focus is in cornea and external diseases as well as refractive surgery.</p><p>After earning his Bachelor of Science in engineering at University of California, Berkeley, in 1986, Dr. Chuck attended Columbia University, earning his Doctor of Medicine and Doctor of Philosophy in 1993. He started his postdoctoral training at St. Mary&rsquo;s Health Center, completing a yearlong internship in internal medicine in 1994. From then until 1998, he pursued a residency in ophthalmology at Washington University and Barnes Hospital, acting as chief resident in his final year. In 1999, he completed a yearlong fellowship in cornea and refractive surgery at Doheny Eye Institute, University of Southern California.</p><p>Dr. Chuck&rsquo;s research has been published in numerous peer-reviewed journals as well as shared through many abstracts, book chapters and podium and poster presentations. He has been an editor and served on the editorial boards of many publications including the <em>Lasers in Surgery and Medicine, Journal of Refractive Surgery, Current Opinion in Ophthalmology and BMC Ophthalmology</em>. He currently serves as the Editor-in-Chief of the major journal <em>ARVO Translational Vision Science and Technology</em> and is a member of the NIH National Eye Institute Council of Editors.</p><p>Dr. Chuck is board certified and is a member of many local, national and international professional societies including the International Society for Refractive Surgery, the American Society for Laser Medicine and Surgery, and the Manhattan Ophthalmological Society. He currently serves as Secretary for Quality of Care for the American Academy of Ophthalmology.</p>

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