Sarah Sungurlu
Asli S. Sucu
Kate R. Steinberg
Melissa R. Stein
<p><strong>Current Investigations</strong></p>
<ol start="1" style=" margin-bottom: 0in;" type="1">
<li>Development of an Objective Structured Clinical Examination (OSCE) in Substance Abuse</li>
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<p> </p>
Brian D. Spund
Luke R. Sponholz
Simon D. Spivack
<p>Focusing diagnostics and therapeutics on those most likely to benefit is a key to successful intervention at both the public health and clinical levels. The translational goal of the Spivack laboratory is to identify individuals at particularly high risk for lung malignancy, and selected non-malignant lung diseases, upon whom to focus smoking/toxin exposure cessation (primary prevention), chemoprevention (secondary prevention), and early disease detection efforts (disease screening, tertiary prevention).</p>
<p>The laboratory is currently exploring individual Gene x Environment signatures as susceptibility markers by exploring quantitative gene (mRNA) expression phenotypes, and the DNA sequence, methylation, microRNA, and other epigenetic features potentially underlying these expression phenotypes, <em>in vitro</em> and in human populations. This is performed in the setting of defined tobacco, diet, and other exposures. There are both mechanistic and translational components to the studies. </p>
<p><br /><strong>Mechanistically</strong>, the role of epigenetic variation in promoter regions in the 5' and 3' regulatory regions of carcinogenesis and oxidant pathway genes is being explored <em>in vitro</em>, using human genomic DNA reporter constructs, and native gene regulation models. High resolution technologies include the realtime quantitation of native mRNA and microRNA by the laboratory's RNA-specific strategy (<em>patented</em>); the tagged-bisulfite genomic sequencing strategy to determine single base resolution CpG methylation status (tBGS, <em>patented</em>); an experimental strategy for assaying microRNA binding to mRNA, for determining the role of miRNA in candidate gene regulation (<em>patented</em>); and evaluation of functional consequences of DNA methylation detail, using a novel patch reporter construct (<em>patented</em>). A new method to engineer methyl-cytosines into the epigenome has recently been developed.</p>
<p>Whole (epi)genome approaches to identify molecular events unique to lung cancer are being completed, which will represent one of the initial cross-platform 'omics level discovery examinations of lung tissues. The execution of each individual discovery platform involves expert local collaborators and cores in (epi)genetics and genomics, and the "integromics" is critically reliant on Einstein strengths in informatics and biostatistical analyses.</p>
<p> </p>
<p><strong>Translationally</strong>, human lung carcinogenesis biomarkers are being established by pairing laser capture microdissected lung with several unique, non-invasively collected surrogate specimens developed in the laboratory. These include mRNA expression signatures from brush-exfoliated buccal mucosa cells, microRNAs detected in exhaled breath condensate representing first reports for a new exhaled airway biomarker class, and exhaled metabolomic signatures. These airway-derived specimens continue to accrue from a sampling (currently n>1000) of a population assembled in a lung cancer case-control context. The specimens are being studied with a view toward developing non-invasive assays in populations.</p>
<p> </p>
<p>The overall aim is to develop informative non-invasive risk profiling, preventive, and early disease detection strategies for the lung in human populations.</p>
<p> </p>
<p> <em>Work is funded by ongoing NIH,</em><em> DoD, and Foundation support.</em></p>
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<p><strong>Clinical Specialties</strong></p>
<ul style="font-size: 1em; color: #333333; padding: 0px; margin: 20px 0px 25px 38px;">
<li style="padding: 0px; margin: 12px 0px 5px 0px;">lung nodule evaluation</li>
<li style="padding: 0px; margin: 12px 0px 5px 0px;">lung cancer diagnostics and screening</li>
<li style="padding: 0px; margin: 12px 0px 5px 0px;">interstitial lung disease</li>
<li style="padding: 0px; margin: 12px 0px 5px 0px;">environmental lung disease</li>
<li style="padding: 0px; margin: 12px 0px 5px 0px;">refractory asthma</li>
<li style="padding: 0px; margin: 12px 0px 5px 0px;">general pulmonary medicine</li>
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Genome-wide surveys of lung epithelia. Translational lung studies. Mechanistic studies in functional epigenetics.
<p class="MsoNormal" style="line-height: 15.6pt;"><span style="font-size: 9.0pt;">A researcher and clinician, Dr. Spivack is developing tests for detecting lung cancer at the earliest possible stage—before it becomes fatal by spreading to other parts of the body. In one of several NIH-funded studies, his laboratory is working on a noninvasive, early-diagnosis test for lung cancer that detects particular genetic elements and chemicals in exhaled breath.</span></p>
<p class="MsoNormal" style="line-height: 15.6pt;"><span style="font-size: 9.0pt;">In addition to general pulmonary medicine, Dr. Spivack’s clinical practice focuses on lung nodule and lung cancer diagnosis, diffuse interstitial lung diseases, and environmental lung diseases.</span></p>
Dr. Spivack specializes in consultative pulmonary medicine, with an emphasis on the evaluation of lung nodules, lung cancer screening, asthma, and environmental and interstitial lung disease.<span style="color:#4d4d4d;font-family:Arial, Helvetica, source-code-pro, Menlo, Monaco, Consolas, 'Courier New', monospace;font-size:16px;background-color:#ffffff;"><strong></strong></span>
Dr. Spivack’s research focuses on the development of non-invasive early detection airway biomarkers of lung cancer risk, as well as epigenetics, gene regulation, gene-environment interaction and non-invasive measurement of deep lung phenomena in humans.
<ol>
<li>Zhenqiu Huang, Alex Maslov, Xiao Dong, Shixiang Sun, Moonsook Lee, Chirag Shah, Ali Sadoughi, Aditi Desai, Dhruv Patel, Taha Siddiqui, Jaiminkumar Patel, Miao Shi, Spencer Waldman, Ava Marsh, Yakov Peter, <strong>*Simon D Spivack,</strong> *Jan Vijg. Somatic Mutations At Single Base Resolution in Single Bronchial Progenitor Cells Collected From Human Lung. <em>(Nature Genetics, April 2022, </em><a href="https://www.nature.com/articles/s41588-022-01035-w" target="_blank">https://www.nature.com/articles/s41588-022-01035-w</a>). (*co-senior authors).</li>
<li>Shi M, Han W, Loudig O, Shah CD, Dobkin JB, Keller S, Sadoughi A, Zhu C, Siegel RE, Fernandez MK, DeLaRosa L, Patel D, Desai A, Siddiqui T, Gombar S, Suh Y, Wang T, Hosgood HD, Pradhan K, Ye K, <strong>Spivack SD.</strong> Initial development and testing of an exhaled microRNA detection strategy for lung cancer case-control discrimination. Sci Rep. 2023 Apr 24;13(1):6620. doi: 10.1038/s41598-023-33698-8. PMID: 37095155; PMCID: PMC10126132.</li>
<li>Yoo EJ, Kim JS, Stransky S, <strong>Spivack S,</strong> Sidoli S. Advances in proteomics methods for the analysis of exhaled breath condensate. Mass Spectrom Rev. 2024 Jul-Aug;43(4):713-722. doi: 10.1002/mas.21871. Epub 2023 Dec 27. PMID: 38149478.</li>
<li>Zefi O, Waldman S, Marsh A, Shi MK, Sonbolian Y, Khulan B, Siddiqui T, Desai A, Patel D, Okorozo A, Khader S, Dobkin J, Sadoughi A, Shah C, <strong>*Spivack S,</strong> *Peter Y. Distinctive field effects of smoking and lung cancer case-control status on bronchial basal cell growth and signaling. Respir Res. 2024 Aug 19;25(1):317. doi: 10.1186/s12931-024-02924-w. PMID: 39160511; PMCID: PMC11334309. *(co-senior authors)</li>
<li>Mitchell MI, Ben-Dov IZ, Ye K, Liu C, Shi M, Sadoughi A, Shah C, Siddiqui T, Okorozo A, Gutierrez M, Unawane R, Biamonte L, Parikh K, <strong>Spivack S,</strong> Loudig O. Exhaled breath condensate contains extracellular vesicles (EVs) that carry miRNA cargos of lung tissue origin that can be selectively purified and analyzed. J Extracell Vesicles. 2024 Apr;13(4):e12440. doi: 10.1002/jev2.12440. Erratum in: J Extracell Vesicles. 2024 May;13(5):e12453. doi: 10.1002/jev2.12453. PMID: 38659349; PMCID: PMC11043690.</li>
<li>Khulan B, Ye K, Shi MK, Waldman S, Marsh A, Siddiqui T, Okorozo A, Desai A, Patel D, Dobkin J, Sadoughi A, Shah C, Gera S, Peter Y, Liao W, *Vijg J, *<strong>Spivack SD</strong>. Normal bronchial field basal cells show persistent methylome-wide impact of tobacco smoking, including in known cancer genes. Epigenetics. 2025 Dec;20(1):2466382. doi: 10.1080/15592294.2025.2466382. Epub 2025 Feb 20. PMID: 39980243; PMCID: PMC11849931. *(co-senior authors)</li>
</ol>
<p>Simon D. Spivack, MD, MPH, is Professor, Medicine, Epidemiology and Genetics at Montefiore Einstein. He is also former Emeritus Chief, Pulmonary Medicine. Clinically, Dr. Spivack specializes in consultative pulmonary medicine, with an emphasis on the evaluation of lung nodules, lung cancer screening, asthma, and environmental and interstitial lung disease. </p><p>After obtaining his Bachelor of Science in Psychobiology from McGill University in Montreal, Canada in 1980, Dr. Spivack earned his Doctor of Medicine from the State University of New York Upstate Medical University in 1985. He then completed an internship and residency in internal medicine at the University of Massachusetts Medical Center in 1988. Dr. Spivack then earned his Master of Public Health at Harvard University, School of Public Health in 1989. He completed a clinical pulmonary and critical care medicine and lung research fellowship at the University of Vermont in 1992. </p><p>Dr. Spivack’s research focuses on the development of non-invasive early detection airway biomarkers of lung cancer risk, as well as epigenetics, gene regulation, gene-environment interaction and non-invasive measurement of deep lung phenomena in humans. His work has been published in numerous peer-reviewed journals, articles, chapters and books, and he has given many national/international presentations, organized symposia and visiting professorships. Dr. Spivack is on the Editorial Board for Scientific Reports and is a reviewer for journals such as <em>PLoS Genetics</em>, <em>Genetics in Medicine</em>, <em>Nature Protocols</em>, <em>American Journal of Respiratory & Critical Care Medicine</em>, <em>Carcinogenesis</em>, <em>Cancer Research</em> and others. He holds multiple United States patents. He has been continually funded by the National Institutes of Health (NIH) for research for over 25 years.
</p><p>Dr. Spivack is board certified in internal medicine, pulmonary medicine and critical care medicine. He is a member of the American Thoracic Society (ATS), the American Association for Cancer Research (AACR) and the American Lung Association (ALA). He is a frequent peer-reviewer on various NIH study sections. In the past, Dr. Spivack won the Excellence in Research Award from ALA and the NIH/National Institute of Environmental Health Sciences (NIEHS) Clinical Scientist Development Award.
</p>
Olena Slinchenkova
Victoria Lynn Shulman
Victoria Shulman, MD, is an attending physician at the Children’s Hospital at Montefiore Einstein and Assistant Professor, Pediatrics at our Albert Einstein College of Medicine. Dr. Shulman’s clinical focus is in pediatric emergency medicine, with a particular area of interest in resident and medical student education. <br /><br />After obtaining her Bachelor of Arts from the City University of New York, Queens College in 1986, Dr. Shulman earned her Doctor of Medicine at Albert Einstein College of Medicine in 1990. She completed her pediatrics internship and residency at Montefiore Einstein in 1994, where she was Chief Resident in her final year. <br /><br />Dr. Shulman’s research aligns with her clinical expertise. Her work has been published in the Journal of Adolescent Health and the Journal of Neurology, as well as chapters in scientific books. <br /><br />Dr. Shulman is board certified by the American Board of Pediatrics. In 1994, she received the Leo M. Davidoff Society Certificate of Distinction for the teaching of medical students. In 2023, Dr. Shulman was inducted as a member of the Leo M. Davidoff Society.<br />