Jeffrey E. Pessin
<p>The Pessin laboratory is analyzing insulin signaling at the molecular level, the regulation of glucose uptake and metabolism at the cellular, molecular level and the integrative systems of metabolism in normal and pathophysiologic states in genetic rodent models. Our efforts have been focused on three major aspects of insulin signaling and insulin sensitivity. These areas include the molecular mechanisms of adipose tissue inflammation leading to fibrosis and programmed cell death, the regulation of insulin/nutriebt signaling in the regulation of liver gluconeogenesis and lipogenesis and there dysregulation in states of insulin resistance.</p>
<p>One major laboratory project is the investigation of adipocyte progenitor cells, adipocyte programmed cell death and adipose tissue fibrosis that is induced by high fat feeding. In these studies, we have utilized a variety of experimental approaches including genetically engineered mice, Fluorescent Activated Cell Sorting (FACS) analyses and sorting along RNA-Seq and single nuclei RNA-Seq. In these analyses we isolated a variety of inflammatory specific cell types within adipose tissue and have taken extensive use of RNAseq technology to characterize the expression profiles of these various cell subsets. This approach has allowed us to develop a functional understanding of the signaling interplay between the adipose tissue immune cell types to determine the specific role each cell is playing in the inflammatory response. In collaboration with the laboratory of Kosaku Shinoda we are exploring the relationship between metabolism, autophagy and energy balance in adipocyte lineage determination (brown, beige and white) as a potential therapeutic approach for both diabetes and obesity. </p>
<p>A second major laboratory project is based upon our recent findings in collaboration with the laboratory of Fajun Yang that in the fed state CDK8/CycC complex directly phosphorylates the nuclear form of SREBP-1c that induces an E3 ligase mediated ubiquitination and proteasome-mediated degradation of SREBP-1c. This process is one of several that is required to maintain nuclear SREBP1-c at very low levels thereby suppresses lipogenic gene expression and lipogenesis. However, n the fed state, CDK8/CycC proteins are rapidly down regulated through a mTORC1 dependent pathway leading to increased SREBP-1c stability and increased lipogenic gene expression and lipogenesis. During the past two years, we have developed a robust research team, several key mouse genetic models, human liver biopsy speciments and cell based approaches to investigate the regulation of liver gluconeogenesis abd lipogenesis in normal and pathophysiologic states of insulin resistance, obesity and non-alcoholic fatty liver disease (NFALD). In these approaches we perform various high-through put DNA sequencing technologies (ie: RNA-seq, single cell RNA-seq, ChIP-seq, 3 dimensional DNA conformation capture (Hi-C) that are used to directly assess the epigenetic basis of normal and pathological liver metabolic funciton.</p>
<p>We have also initiated new studies to examine the development of heart failure in diabetic cardiomyopathy. New data from the laboratory indicates that increasing glycolytic rate in cardiomyocytes markedly protects the heart from myocardial infarction. In collaboration with the laboratory of Gaetano Santulli, we are examining the mechanistic basis for this novel observation as a means to specifcally prevent heart damage and failure that progressively occurs following myocardial infarction.</p>
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Epigenetic modifications regulating metabolism
Regulation of lipogenic gene transcription and de novo lipogenesis
Cardiometabolic health
adipocyte and liver biology
Integrative metabolic signaling
<p class="MsoNormal" style="line-height: 15.6pt;"><span style="font-size: 9.0pt;">Dr. Pessin directs the Einstein-Mount Sinai Diabetes Research Center, one of only sixteen NIH-funded diabetes centers of its kind in the country. He guides the research of more than 90 scientists investigating type 1 (formerly juvenile) and type 2 (formerly adult-onset) diabetes. The center also includes training programs and community-based activities in the Bronx. Dr. Pessin’s own research focuses on insulin signaling and the mechanisms contributing to the onset of type 1 diabetes.</span></p>
<p class="MsoNormal" style="line-height: 15.6pt;"><span style="font-size: 9.0pt;">Dr. Pessin also studies how adult progenitor cells (cells that have the capacity to differentiate into a specific cell type) influence the development of fat tissue and how mechanical signals influence stem cell development. The findings from such research have led to animal models for studying insulin resistance and diabetes.</span></p>
<p class="MsoNormal" style="line-height: 15.6pt;"><span style="font-size: 9.0pt;">Dr. Pessin is associate editor of Diabetes, the peer-reviewed journal of the American Diabetes Association, and the former editor-in-chief of<span> </span><em>Endocrinology</em><span> </span>and the <em>American Journal of Physiology - Endocrinology and Metabolism</em>. He has received the Eli Lilly Outstanding Investigator Award of the American Diabetes Association and the Mary Jane Kugel Award of the Juvenile Diabetes Research Foundation International.</span></p>
<p class="MsoNormal" style="margin: 0in; font-size: 12pt; font-family: Calibri, sans-serif;"><span style="font-family: 'Times New Roman', serif;"><a href="https://pubmed.ncbi.nlm.nih.gov/33812059/"><span style="color: #0071bc;">The Mediator complex kinase module is necessary for fructose regulation of liver glycogen levels through induction of glucose-6-phosphatase catalytic subunit (G6pc).</span></a></span></p>
<p class="MsoNormal" style="margin: 0in; font-size: 12pt; font-family: Calibri, sans-serif;"><span style="font-family: 'Times New Roman', serif; color: #212121;">Youn DY, Xiaoli AM, Zong H, Okada J, Liu L, Pessin J, <strong>Pessin JE</strong>, Yang F.</span><span style="font-family: 'Times New Roman', serif; color: #4d8055;">Mol Metab. 2021 Jun;48:101227. doi: 10.1016/j.molmet.2021.101227. Epub 2021 Mar 31.PMID: 33812059 </span></p>
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<p class="MsoNormal" style="margin: 0in; font-size: 12pt; font-family: Calibri, sans-serif;"><span style="font-family: 'Times New Roman', serif;"><a href="https://pubmed.ncbi.nlm.nih.gov/33667344/"><span style="color: #0071bc;">Conversion of the death inhibitor ARC to a killer activates pancreatic β cell death in diabetes.</span></a></span></p>
<p class="MsoNormal" style="margin: 0in; font-size: 12pt; font-family: Calibri, sans-serif;"><span style="font-family: 'Times New Roman', serif; color: #212121;">McKimpson WM, Chen Y, Irving JA, Zheng M, Weinberger J, Tan WLW, Tiang Z, Jagger AM, Chua SC Jr, <strong>Pessin JE</strong>, Foo RS, Lomas DA, Kitsis RN.</span><span style="font-family: 'Times New Roman', serif; color: #4d8055;">Dev Cell. 2021 Mar 22;56(6):747-760.e6. doi: 10.1016/j.devcel.2021.02.011. Epub 2021 Mar 4.PMID: 33667344</span></p>
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<p class="MsoNormal" style="margin: 0in; font-size: 12pt; font-family: Calibri, sans-serif;"><span style="font-family: 'Times New Roman', serif;"><a href="https://pubmed.ncbi.nlm.nih.gov/32848017/"><span style="color: #0071bc;">ATG16L1 autophagy pathway regulates BAX protein levels and programmed cell death.</span></a></span></p>
<p class="MsoNormal" style="margin: 0in; font-size: 12pt; font-family: Calibri, sans-serif;"><span style="font-family: 'Times New Roman', serif; color: #212121;">Chen F, Amgalan D, Kitsis RN, <strong>Pessin JE</strong>, Feng D.</span><span style="font-family: 'Times New Roman', serif; color: #4d8055;">J Biol Chem. 2020 Oct 30;295(44):15045-15053. doi: 10.1074/jbc.RA120.013999. Epub 2020 Aug 26.PMID: 32848017 </span></p>
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<p class="MsoNormal" style="margin: 0in; font-size: 12pt; font-family: Calibri, sans-serif;"><span style="font-family: 'Times New Roman', serif;"><a href="https://pubmed.ncbi.nlm.nih.gov/32635651/"><span style="color: #0071bc;">The Impact of Single-Cell Genomics on Adipose Tissue Research.</span></a></span></p>
<p class="MsoNormal" style="margin: 0in; font-size: 12pt; font-family: Calibri, sans-serif;"><span style="font-family: 'Times New Roman', serif; color: #212121;">Deutsch A, Feng D, <strong>Pessin JE</strong>, Shinoda K.</span><span style="font-family: 'Times New Roman', serif; color: #4d8055;">Int J Mol Sci. 2020 Jul 5;21(13):4773. doi: 10.3390/ijms21134773.PMID: 32635651 </span></p>
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<p class="MsoNormal" style="margin: 0in; font-size: 12pt; font-family: Calibri, sans-serif;"><span style="font-family: 'Times New Roman', serif;"><a href="https://pubmed.ncbi.nlm.nih.gov/32570757/"><span style="color: #0071bc;">FAM83G Is a Novel Inducer of Apoptosis.</span></a></span></p>
<p class="MsoNormal" style="margin: 0in; font-size: 12pt; font-family: Calibri, sans-serif;"><span style="font-family: 'Times New Roman', serif; color: #212121;">Okada J, Sunaga N, Yamada E, Saito T, Ozawa A, Nakajima Y, Okada K, <strong>Pessin JE</strong>, Okada S, Yamada M.</span><span style="font-family: 'Times New Roman', serif; color: #4d8055;">Molecules. 2020 Jun 18;25(12):2810. doi: 10.3390/molecules25122810.PMID: 32570757 </span></p>
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<p class="MsoNormal" style="margin: 0in; font-size: 12pt; font-family: Calibri, sans-serif;"><span style="font-family: 'Times New Roman', serif;"><a href="https://pubmed.ncbi.nlm.nih.gov/32075912/"><span style="color: #0071bc;">Regulation of gene expression during the fasting-feeding cycle of the liver displays mouse strain specificity.</span></a></span></p>
<p class="MsoNormal" style="margin: 0in; font-size: 12pt; font-family: Calibri, sans-serif;"><span style="font-family: 'Times New Roman', serif; color: #212121;">Chi Y, Youn DY, Xiaoli AM, Liu L, Pessin JB, Yang F, <strong>Pessin JE.</strong></span><span style="font-family: 'Times New Roman', serif; color: #4d8055;">J Biol Chem. 2020 Apr 10;295(15):4809-4821. doi: 10.1074/jbc.RA119.012349. Epub 2020 Feb 19.PMID: 32075912 </span></p>
<p class="MsoNormal" style="margin: 0in; font-size: 12pt; font-family: Calibri, sans-serif; vertical-align: top;"><span style="font-family: 'Times New Roman', serif; color: #5b616b;">7</span></p>
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<p class="MsoNormal" style="margin: 0in; font-size: 12pt; font-family: Calibri, sans-serif;"><span style="font-family: 'Times New Roman', serif;"><a href="https://pubmed.ncbi.nlm.nih.gov/32051343/"><span style="color: #0071bc;">SNAP23 depletion enables more SNAP25/calcium channel excitosome formation to increase insulin exocytosis in type 2 diabetes.</span></a></span></p>
<p class="MsoNormal" style="margin: 0in; font-size: 12pt; font-family: Calibri, sans-serif;"><span style="font-family: 'Times New Roman', serif; color: #212121;">Liang T, Qin T, Kang F, Kang Y, Xie L, Zhu D, Dolai S, Greitzer-Antes D, Baker RK, Feng D, Tuduri E, Ostenson CG, Kieffer TJ, Banks K, <strong>Pessin JE</strong>, Gaisano HY.</span><span style="font-family: 'Times New Roman', serif; color: #4d8055;">JCI Insight. 2020 Feb 13;5(3):e129694. doi: 10.1172/jci.insight.129694.PMID: 32051343 </span></p>
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<p class="MsoNormal" style="margin: 0in; font-size: 12pt; font-family: Calibri, sans-serif;"><span style="font-family: 'Times New Roman', serif;"><a href="https://pubmed.ncbi.nlm.nih.gov/31979355/"><span style="color: #0071bc;">Dapagliflozin Inhibits Cell Adhesion to Collagen I and IV and Increases Ectodomain Proteolytic Cleavage of DDR1 by Increasing ADAM10 Activity.</span></a></span></p>
<p class="MsoNormal" style="margin: 0in; font-size: 12pt; font-family: Calibri, sans-serif;"><span style="font-family: 'Times New Roman', serif; color: #212121;">Okada J, Yamada E, Saito T, Yokoo H, Osaki A, Shimoda Y, Ozawa A, Nakajima Y, <strong>Pessin JE</strong>, Okada S, Yamada M.</span><span style="font-family: 'Times New Roman', serif; color: #4d8055;">Molecules. 2020 Jan 23;25(3):495. doi: 10.3390/molecules25030495.PMID: 31979355 </span></p>