Lung Disease | Montefiore Einstein

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).
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, in vitro 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. 
 Mechanistically, the role of epigenetic variation in promoter regions in the 5' and 3' regulatory regions of carcinogenesis and oxidant pathway genes is being explored in vitro, 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 (patented); the tagged-bisulfite genomic sequencing strategy to determine single base resolution CpG methylation status (tBGS, patented);  an experimental strategy for assaying microRNA binding to mRNA, for determining the role of miRNA in candidate gene regulation (patented); and evaluation of functional consequences of DNA methylation detail, using a novel patch reporter construct (patented).  A new method to engineer methyl-cytosines into the epigenome has recently been developed.
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.
 
Translationally, 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.
 
The overall aim is to develop informative non-invasive risk profiling, preventive, and early disease detection strategies for the lung in human populations.
 
 Work is funded by ongoing NIH, DoD, and Foundation support.
 
Clinical Specialties
<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>
</ul>

Research Areas

Development of early lung cancer detection strategies; exhaled nucleic acid and other airway biomarkers.
Genome-wide surveys of lung epithelia. Translational lung studies. Mechanistic studies in functional epigenetics.

Expert Tags

Pulmonology

Lung Disease

Lung Cancer

Areas of Expertise

Interstitial lung disease

Lung nodule evaluation

Lung toxicology

Expert Summary

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.
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.

Research Profile

https://einsteinmed.edu/faculty/11003/Simon-Spivack

Clinical Profile

https://montefioreeinstein.org/profiles/1366438475/simon-d-spivack

CHAM Provider

Off

Professional Title

M.D.

M.P.H.

Clinical Focus

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.

Research Focus

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.

Elsevier Profile

https://einstein.pure.elsevier.com/en/persons/efede15b-e8c0-4800-9956-2b3e7aabd…

Selected Publications

Selected Publications, as of April, 2023:
Shi M, Han W, Loudig O, Shah C, Dobkin J, Keller S, Sadoughi A, Patel D, Desai A, Gombar S, Suh Y, Fernandez MK, DeLaRosa L, Wang T, Hosgood D, Pradhan K, Ye K, Spivack SD.  (2023) Initial development and testing of an exhaled microRNA detection strategy for lung cancer case-control discrimination. [accepted, Scientific Reports, NPG]
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<p class="MsoNormal" style="margin-bottom: 1.7pt; background-image: initial; background-position: initial; background-size: initial; background-repeat: initial; background-attachment: initial; background-origin: initial; background-clip: initial;"><span style="color: #212121; background-image: initial; background-position: initial; background-size: initial; background-repeat: initial; background-attachment: initial; background-origin: initial; background-clip: initial;">Huang Z, Sun S, Lee M, Maslov AY, Shi M, Waldman S, Marsh A, Siddiqui T, Dong X, Peter Y, Sadoughi A, Shah C, Ye K, *Spivack SD, *Vijg J. Single-cell analysis of somatic mutations in human bronchial epithelial cells in relation to aging and smoking. Nat Genet. 2022 Apr;54(4):492-498. doi: 10.1038/s41588-022-01035-w. Epub 2022 Apr 11. PMID: 35410377. (*co-senior authors).
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 Cleven KL, Ye K, Zeig-Owens R, Hena KM, Montagna C, Shan J, Hosgood HD 3rd, Jaber N, Weiden MD, Colbeth HL, Goldfarb DG, Spivack SD++, Prezant DJ++ (++co-senior authors). <a href="https://www.ncbi.nlm.nih.gov/pubmed/31126090">Genetic Variants Associated with FDNY WTC-Related Sarcoidosis.</a> Int J Environ Res Public Health. 2019 May 23;16(10). pii: E1830. doi: 10.3390/ijerph16101830. PMID:31126090.
Dong X, ShiN, LeeM, ToroR, Gravina S, Han W, Yasuda S, Wang T, Zhang Z, Vijg J, Suh Y, Spivack SD. (2018) Global, integrated analysis of methylomes and transcriptomes from laser capture microdissected bronchial and alveolar cells in human lung. Epigenetics 10.1080/15592294.2018.1441650, 2018.
Mullapudi N, Ye B, Suzuki M, Wang T, Fazarri M, Han W, Shi M, Marquardt G, Lin J, Wang T, Keller S, Zhu C, Locker J,  Spivack SD. Genome-wide methylome alterations in lung cancer  PLoS ONE, Dec. 2015.
Lin J, Marquardt G, Mullapudi N, Wang, T, Han W, Shi W, Zhu C, Keller S, Zhu C, Locker J, Spivack SD. Lung cancer transcriptomes refined with laser capture microdissection. Am J Pathology 06.028. 2014 .
Han W, Shi M, Spivack SD. Site-specific methylated reporter constructs for functional analysis of DNA methylation. Epigenetics 4; 8(11), 2013.
Shi M, Han W, Spivack SD. A quantitative method to identify miRNAs targeting an mRNA using a 3'UTR RNA affinity technique. Analytic Biochem 1;443(1):1-12, 2013.
Alberg AJ, Brock MV, Ford JG, Samet JM, Spivack, SD.  Epidemiology of lung cancer.  In Evidence-based Practice Guidelines. Diagnosis and Management of Lung Cancer (ACCP position statement). CHEST.  May 2013;143(5 Suppl):e1S-e29S. doi: 10.1378/chest.12-2345. PMID: 23649439.
Tan XT, Marquardt G, Shi M, Han W, Spivack SD. High throughput library screening identifies phytochemical inducers of phase II mutagen/oxidant metabolism enzymes GSTP1 and NQO1 in human lung cells. Am J Resp Cell Molec Biol, 46(3): 365-71, 2012.
Brock GJ, Moschos S, Spivack SD, Hurteau GJ. The 3' prime paradigm of the miR-200 family and other microRNAs. Epigenetics (6:3, 1-5), 2011.
Tan XT,  Shi M,  Minna JD,  Han W,  Spivack SD. Candidate phytopreventive agent modulation of phase II metabolism enzymes GSTP1 and NQO1 in human bronchial cells. J Nutrition, 140(8): 1404-10, 2010.
Tan, XT,   Wang T,  Xiong S,  Kumar SV,  Han W,  Spivack SD.  Smoking-related gene expression in laser capture microdissected human lung. Clin Cancer Res, 15(24): 7562-70, 2009.
Han W, Tang T, Reilly AA, Keller S, Spivack SD. Gene promoter methylation analyses from exhaled breath, with differences in smokers and lung cancer cases.  Resp Res, 10:86 epubl, 2009.
Tan X-L,  Moslehi R, Han W, Spivack SD. Haplotype tagging single nucleotide polymorphisms in the glutathione S-transferase P1 gene promoter and susceptibility to lung cancer. Cancer Detection Prev,32:403-415, 2009.
Tan X-L,  Spivack SD. Dietary chemoprevention strategies for induction of phase II metabolism: a review. Lung Cancer,65(2):129-37, 2009.
Hurteau GJ, Carlson AJ, Spivack, SD, Brock GJ. Restoration of E-Cadherin expression by over-expression of the microRNA hsa-miR-200c via reduced expression of the transcription factor TCF8. Cancer Res. 67:7972-76, 2007.
Hurteau, GJ, Spivack SD, Brock G.  Parallel identification of miRNA and target mRNA by combined informatics and qRT-PCR approaches: application to has-miR-200c.  Cell Cycle 5(17):1951-56, 2006.
Han W, Cauchi S, Herman JG, Spivack SD.  Methylation mapping of DNA by tag-modified bisulfite genomic DNA sequencing. Analytic Biochem. 355: 50-61, 2006.
Cauchi S, Han W, Kumar SV, Spivack SD. Haplotype-environment interactions regulating the human GSTP1 promoter Cancer Res. 66(12): 6439-6448, 2006.
Kumar SV, Hurteau GJ, Spivack SD. Validity of mRNA expression analyses of human saliva. Clin. Cancer Res. 12: 5033-39, 2006.
Spivack SD, Hurteau GJ, Jain R, Kumar SV, Aldous KM, Gierthy JF, Kaminsky LS.  Gene-environment interaction signatures by quantitative mRNA profiling in exfoliated buccal mucosal cells. Cancer Res, 64:6805-6813, 2004.
Spivack SD, Hurteau GJ, Fasco MJ, Kaminsky LS.  Phase I and II carcinogen metabolism gene expression in human lung tissue and tumors.  Clinical Cancer Research, 9:6002-6011, 2003.

EMR ID

4969

Biography

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. 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. 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 PLoS Genetics, Genetics in Medicine, Nature Protocols, American Journal of Respiratory & Critical Care Medicine, Carcinogenesis, Cancer Research 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.
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.

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