Director Of Research, Emergency Medicine
Education and Training
1975 B.A., Biology, University of Rochester, Rochester, N.Y.
1981 M.D., University of Rochester
1981 Ph.D., Microbial Physiology, University of Rochester
Postgraduate Education and Training:
1981 - 1982 Internship, Internal Medicine, University of Maryland, Baltimore, MD
1982 - 1984 Residency, Emergency Medicine, UCLAHospital and Clinics, Los Angeles, CA
1982 - 1984 Fellowship, Undersea & Hyperbaric Medicine, MemorialMedicalCenterLong Beach, CA
|INSTITUTION AND LOCATION||DEGREE (if applicable)||Completion Date MM/YYYY||FIELD OF STUDY|
|University of Rochester, Rochester, NY||BA||05/1975||Biology|
|University of Rochester, Rochester, NY||MD||05/1981||Medicine|
|University of Rochester, Rochester, NY||PHD||05/1981||Microbiology|
|University of Maryland, Baltimore, Baltimore, MD||Other training||06/1982||Internal Medicine|
|University of California, Los Angeles, Los Angeles, CA||Resident||06/1984||Emergency Medicine|
A. PERSONAL STATEMENT Dr. Thom is a Professor of Emergency Medicine at the University of Maryland. He is board certified in emergency medicine and undersea & hyperbaric medicine. Dr. Thom’s training includes a PhD in microbial physiology. His research awards have been focused on biochemical and physiological responses to oxidative stress with a particular focus on the impact of high pressure gases. B. POSITIONS AND HONORS
Positions and Employment
|1984 - 1986||Assistant Professor of Microbiology, University of Colorado, Denver, CO|
|1984 - 1986||Emergency Medicine Physician, Hyperbaric Medicine Director, Porter Memorial Hospital, Denver, CO|
|1986 - 1994||Assistant Professor of Medicine, University of Pennsylvania, Philadelphia, PA|
|1986 - 2013||Chief, Hyperbaric Medicine, Institute for Environmental Medicine, University of Pennsylvania, Philadelphia, PA|
|1994 - 1995||Assistant Professor of Emergency Medicine, University of Pennsylvania, Philadelphia, PA|
|1995 - 2003||Associate Professor of Emergency Medicine, University of Pennsylvania, Philadelphia, PA|
|1997 - 2003||Associate Professor, Emergency Medicine in Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA|
|2003 - 2013||Professor, Emergency Medicine in Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA|
|2003 - 2013||Professor of Emergency Medicine, University of Pennsylvania, Philadelphia, PA|
|2013 -||Professor of Emergency Medicine, University of Maryland, Baltimore, Baltimore, MD|
Other Experience and Professional Memberships
|-||Editorial Board, Annals of Emergency Medicine; Undersea and Hyperbaric Medicine|
|-||Ad hoc Reviewer, American Journal of Physiology, Archives of Biochemistry and Biophysics, Archives of Pediatrics & Adolescent Medicine, Biochemica Biophysica Acta, Clinical Toxicology, Journal of Applied Physiology, Journal of Clinical Investigation, Journal of Leukocyte Biology, Journal of Neurology, Neurosurgery, Psychiatry, Journal of Toxicology and Environmental Health, The Lancet, Proceedings of the National Academy of Sciences USA|
|1986 -||Member, Undersea and Hyperbaric Medical Society, Hyperbaric Oxygen Therapy Committee and Research Committee|
|1987 - 1990||Member, American College of Emergency Physicians Research Committee|
|1998 - 2000||Member, U.S. Environmental Protection Agency, Advisory Committee on Air Quality Criteria for Carbon Monoxide|
|2001 -||Member, Curriculum Rev. Committee for Dept. of Military and Emerg. Med., Uniformed Services Univ. of the Health Sciences|
|2001 - 2002||Grant Review, Office of Naval Research, Medical Science & Technology (S & T)|
|2003 - 2003||Member, Study Section, National Institutes of Health, NIEHS Program on Advanced Research Cooperation in Environmental Health Sciences. Special Emphasis Panel|
|2003 - 2003||Member, NCCAM|
|2006 - 2006||Grant Reviewer, Office of Naval Research, Medical Science & Technology (S & T)|
|2009 - 2009||Member, NHLBI|
|1980||Sherman Award, N.Y. American Society for Microbiology|
|1981||Outstanding Scientific Contributions to Advances in the Undersea or Hyperbaric Medical Field, Sigma Xi|
|1988||Edgar End Award, Gulf Coast Chapter of the Undersea and Hyperbaric Medical Society|
|1996||Albert R. Behnke Award, Undersea and Hyperbaric Medical Society (UHMS)|
|1998||C. Longoni Award, Italian Undersea and Hyperbaric Medical Society|
|2007||Paul Bert Award, Undersea and Hyperbaric Medical Society|
|2008||Hyperbaric Research Prize, International Baromedical Research Foundation|
|2008||Albert R. Behnke Award, Undersea and Hyperbaric Medical Society|
C. Contribution to Science
- One of my early career interests came from clinical experiences evaluating and treating patients with carbon monoxide poisoning. Clinical observations made it clear that pathophysiology went beyond the hypoxic stress associated with carboxyhemoglobin. I developed an animal model based on the known high-risk factors for so-called delayed neurological sequelae. I also carried out clinical studies looking for plasma biomarkers of high-risk poisoning and organized the first prospective randomized clinical trial in the United States examining the efficacy for hyperbaric oxygen therapy for acute carbon monoxide poisoning. The work has results in a view that brain injury mediated by CO is an immune response to modified proteins. Others have recently shown elevations in these proteins in the cerebral spinal fluid of CO poisoned patients manifesting neurological sequelae. Below are listed four representative publications from 33 published on this and related subjects.
- Thom SR, Taber RL, Mendiguren II, Clark JM, Hardy KR, Fisher AB. Delayed neuropsychologic sequelae after carbon monoxide poisoning: prevention by treatment with hyperbaric oxygen. Ann Emerg Med. 1995 Apr;25(4):474-80. PubMed PMID: 7710151.
- Thom SR, Bhopale VM, Fisher D, Zhang J, Gimotty P. Delayed neuropathology after carbon monoxide poisoning is immune-mediated. Proc Natl Acad Sci U S A. 2004 Sep 14;101(37):13660-5. PubMed PMID: 15342916; PubMed Central PMCID: PMC518809.
- Thom SR, Bhopale VM, Han ST, Clark JM, Hardy KR. Intravascular neutrophil activation due to carbon monoxide poisoning. Am J Respir Crit Care Med. 2006 Dec 1;174(11):1239-48. PubMed PMID: 16931637; PubMed Central PMCID: PMC2648106.
- Thom SR, Bhopale VM, Milovanova TM, Hardy KR, Logue CJ, Lambert DS, Troxel AB, Ballard K, Eisinger D. Plasma biomarkers in carbon monoxide poisoning. Clin Toxicol (Phila). 2010 Jan;48(1):47-56. PubMed PMID: 20095814; PubMed Central PMCID: PMC3941305.
- Interest in oxidative stress responses led me to hypothesize that exposure to hyperbaric oxygen would trigger mobilization of vasculogenic stem cells from the bone marrow. From the very first paper on this idea, studies have involved animal models and translational work demonstrating that findings were similar in humans. This has resulted in a much broader examination of clinical variables in wound healing, and studies on the role of stem cells. Below are listed four representative publications from 17 published on this and related subjects.
- Thom SR, Bhopale VM, Velazquez OC, Goldstein LJ, Thom LH, Buerk DG. Stem cell mobilization by hyperbaric oxygen. Am J Physiol Heart Circ Physiol. 2006 Apr;290(4):H1378-86. PubMed PMID: 16299259.
- Milovanova TN, Bhopale VM, Sorokina EM, Moore JS, Hunt TK, Hauer-Jensen M, Velazquez OC, Thom SR. Hyperbaric oxygen stimulates vasculogenic stem cell growth and differentiation in vivo. J Appl Physiol (1985). 2009 Feb;106(2):711-28. PubMed PMID: 19023021; PubMed Central PMCID: PMC2644249.
- Thom SR, Milovanova TN, Yang M, Bhopale VM, Sorokina EM, Uzun G, Malay DS, Troiano MA, Hardy KR, Lambert DS, Logue CJ, Margolis DJ. Vasculogenic stem cell mobilization and wound recruitment in diabetic patients: increased cell number and intracellular regulatory protein content associated with hyperbaric oxygen therapy. Wound Repair Regen. 2011 Mar-Apr;19(2):149-61. PubMed PMID: 21362081; PubMed Central PMCID: PMC3086729.
- Fukaya E, Margolis DJ, Miller CJ, Milovanova TN, Papadopoulos M, Thom SR. Endothelial progenitor cell mobilization following acute wound injury. Wound Repair Regen. 2013 Nov-Dec;21(6):907-8. PubMed PMID: 24134645; PubMed Central PMCID: PMC4007264.
- A paradoxical observation that elevated oxygen partial pressures temporarily inhibit neutrophil β2 integrin adhesion molecules in animal models and in humans led me to a broad examination of clinical responses and also fundamental cell biology and biochemical investigations on how cells regulate β2 integrin adhesion. This phenomenon has relevance to basic physiology, pathophysiology and therapeutic interventions. Below are listed four representative publications from 19 on neutrophil β2 integrins and endothelial adherence.
- Thom SR, Mendiguren I, Hardy K, Bolotin T, Fisher D, Nebolon M, Kilpatrick L. Inhibition of human neutrophil beta2-integrin-dependent adherence by hyperbaric O2. Am J Physiol. 1997 Mar;272(3 Pt 1):C770-7. PubMed PMID: 9124510.
- Thom SR, Bhopale VM, Mancini DJ, Milovanova TN. Actin S-nitrosylation inhibits neutrophil beta2 integrin function. J Biol Chem. 2008 Apr 18;283(16):10822-34. PubMed PMID: 18283105.
- Thom SR, Bhopale VM, Milovanova TN, Yang M, Bogush M, Buerk DG. Nitric-oxide synthase-2 linkage to focal adhesion kinase in neutrophils influences enzyme activity and β2 integrin function. J Biol Chem. 2013 Feb 15;288(7):4810-8. PubMed PMID: 23297409; PubMed Central PMCID: PMC3576086.
- Bhopale VM, Yang M, Yu K, Thom SR. Factors associated with nitric oxide-mediated beta-2 integrin inhibition of neutrophils. J. Biol. Chem. 2015 Jul 10;290(28):17474-84. PubMed PMID: 26032418
- Since the first research I performed working on my PhD, results have shown that exposures to high pressure gases yield responses that cannot be anticipated based on established pathophysiological principles. In short, so-called inert gases appear to exacerbate oxygen toxicity. This work has been developed over the years to document new biochemical responses in cells and animal models. More recently, studies have shown similar responses occur in human cells and in vivo when humans are exposed to high pressure. Below are listed four representative publications from 16 on this and related subjects.
- Thom SR. Inert gas enhancement of superoxide radical production. Arch Biochem Biophys. 1992 Jun;295(2):391-6. PubMed PMID: 1316738.
- Thom SR, Bhopale VM, Yang M. Neutrophils generate microparticles during exposure to inert gases due to cytoskeletal oxidative stress. J Biol Chem. 2014 Jul 4;289(27):18831-45. PubMed PMID: 24867949; PubMed Central PMCID: PMC4081925.
- Yang M, Barak OF, Dujic Z, Madden D, Bhopale VM, Bhullar J, Thom SR. Microparticle and neutrophil activation in SCUBA divers: an oxidative stress response. American journal of physiology. Regulatory, integrative and comparative physiology. Forthcoming;
- Yang M, Bhopale VM, Thom SR. Ascorbic acid abrogates microparticle generation and vbascular injuries associated with high pressure exposure. Journal of applied physiology. Forthcoming;
- Our work on biochemical effects of inert gases led to identification of microparticle formation as an oxidative stress response. This work has led to a new perspective on decompression sickness. While it is relatively rare, decompression sickness is an international problem that few physicians are trained to recognize or manage. It is a systemic disorder long thought to be caused by gas bubbles. However, because asymptomatic bubbles are often found after deep sea diving, additional factors have been sought. We have documented roles for circulating microparticles, vesicular structures with diameters of 0.1 to 1.0 µm, in decompression sickness pathophysiology. This work opens the way for better diagnostic tests and, because interventions directed at microparticles are successful in animals, may lead to novel and more effective treatments. Below are listed four representative publications from 16 on this and related subjects.
- Martin JD, Thom SR. Vascular leukocyte sequestration in decompression sickness and prophylactic hyperbaric oxygen therapy in rats. Aviat Space Environ Med. 2002 Jun;73(6):565-9. PubMed PMID: 12056672.
- Thom SR, Yang M, Bhopale VM, Huang S, Milovanova TN. Microparticles initiate decompression-induced neutrophil activation and subsequent vascular injuries. J Appl Physiol (1985). 2011 Feb;110(2):340-51. PubMed PMID: 20966192.
- Thom SR, Milovanova TN, Bogush M, Yang M, Bhopale VM, Pollock NW, Ljubkovic M, Denoble P, Madden D, Lozo M, Dujic Z. Bubbles, microparticles, and neutrophil activation: changes with exercise level and breathing gas during open-water SCUBA diving. J Appl Physiol (1985). 2013 May 15;114(10):1396-405. PubMed PMID: 23493363.
- Yang M, Kosterin P, Salzberg BM, Milovanova TN, Bhopale VM, Thom SR. Microparticles generated by decompression stress cause central nervous system injury manifested as neurohypophysial terminal action potential broadening. J Appl Physiol (1985). 2013 Nov;115(10):1481-6. PubMed PMID: 24052032; PubMed Central PMCID: PMC3841824.
Complete List of Published Work in My Bibliography:
Microparticles, Hyperbaric gas physiology, beta-2 integrins, vasculogenic stem cells
Thom, S.R., Yang, M. Bhopale, V.M., Milovanova, T.M., Bogush, M., Buerk, D.G. Intra-microparticle nitrogen dioxide is a bubble nucleation site leading to decompression - induced neutrophil activation and vascular injury. J. Appl. Physiol. 2013; 114: 550-558.
Thom, S.R., Bhopale, V.M., Milovanova, T.N., Yang, M., Bogush, M. Nitric oxide synthase-2 linkage to focal adhesion kinase in neutrophils influences enzyme activity and b2 integrin function. J. Biol. Chem. 2013; 288: 4810-4818.
Thom, S.R., Bhopale, V.M., Yang, M. Neutrophils generate microparticles during exposure to inert gases due to cytoskeletal oxidative stress. J. Biol. Chem. 2014; 289: 18831-18845
Thom, S.R., Bennett, M., Banham, N.D., Chin, W., Blake, D.F., Rosen, A., Pollock, N.W., Madden, D., Barak, O., Marroni, A., Balestra, C., Germonpre, P., Pieri, M., Cialoni, D., Le, P.N., Logue, C., Lambert, D., Hardy, K.R., Sward, D., Yang, M., Bhopale, V.B., Dujic, Z. Association of microparticles and neutrophil activation with decompression sickness. J Appl Physiol. 2015; 119:427-434.
Thom, S.R., Hampton, M., Troiano, M.A., Mirza, Z., Malay, D.S., Shannon, S., Jennato, N.B., Donohue, C.M., Hoffstad, O., Woltereck, D., Yang, M., Yu, K., Bhopale, V.M., Kovtun, S., Margolis, D.J. Measurements of CD34+/CD45-dim stem cells predict healing of diabetic neuropathic wounds. Diabetes. 2016; 65: 486-497.
Complete List of Published Work in My Bibliography:
Research interests include:
Production mechanisms and pathophysiology of microparticles.
Mobilization and function of vasculogenic stem cells.
Pathophysiology of decompression sickness.
Mechanisms of action of carbon monoxide in health and disease.
Honors and Awards:
1980 Sherman Award - N.Y. American Society for Microbiology outstanding graduate student research
1981 Sigma Xi
1988 Edgar End Award - from the Gulf Coast Chapter of the Undersea and Hyperbaric Medical Society, "for outstanding research in hyperbaric medicine"
1996 Albert R. Behnke Award from the Undersea and Hyperbaric Medical Society, for "outstanding scientific contributions to advances in the undersea or hyperbaric medical field - carbon monoxide vascular injury and HBO2 effects".
1998 C. Longoni Award from the Italian Undersea and Hyperbaric Medical Society, for “outstanding scientific contributions to undersea and hyperbaric medicine”
2007 Paul Bert Award from the Undersea and Hyperbaric Medical Society, for ”excellence in the practice of hyperbaric medicine and basic research”
2008 Hyperbaric Research Prize from an international scientific panel of the Baromedical Research Foundation, for “basic science contributions that have provided a vital foundation for the practice of hyperbaric medicine”
2008 Albert R. Behnke Award from the Undersea and Hyperbaric Medical Society, for "outstanding scientific contributions to advances in the undersea or hyperbaric medical field - bone marrow stem cell HBO2 effects"
2011 President’s Award, Undersea & Hyperbaric Med. Society – scientific presentation.
2012 President’s Award, Undersea & Hyperbaric Med. Society – scientific presentation.
2013 President’s Award, Undersea & Hyperbaric Med. Society – scientific presentation
Ongoing Research Support
R01 DK94260, NIH
Thom, Stephen/Margolis, David (PI)
Stem cell mobilization in diabetes
This project examines variations in circulating and wound margin stem cells in diabetics and their association with wound healing.
150049, Wyle Integrated Science and Engineering Group
Kochunov, Peter (PI)
QUASAR Acute MRI Changes in Association with Single Hypoxic Exposure
To evaluate possible pathophysiology of altitude cerebral decompression sickness. This study involves exposing human volunteers to decompression to simulated altitude (hypobaric) conditions as done regularly by USAF personnel with and without concomitant hypoxia. Pre- vs. post- exposure studies include high resolution MRI, circulating cytokines and changes will be correlated with circulating microparticles, neutrophil and platelet activation.
N00014-13-1-0614, Office of Naval Research
Thom, Stephen (PI)
Microparticle production with decompression stress in humans
This project examines the microparticle production and neutrophil activation in humans performing experimental SCUBA dives and in injured divers who are suffering from decompression sickness.
N00014-13-1-0613, Office of Naval Research
Thom, Stephen (PI)
Microparticle, platelet-neutrophil aggregation and decompression sickness
The project examines perivascular oxidative stress and the role of microparticles in decompression stress.
N00014-14-1-0094 , Office of Naval Research
Thom, Stephen (PI)
Pharmacological inhibition of neutrophil adherence by nitric oxide
This grant is to elucidate mechanisms for inhibition of murine neutrophil β2 integrins by nitric oxide.
R01 GM103591 , Universtiy of Pennsylvania/NIH
Wu, Gary (PI)
Host-microbial interactions in the gut oxygen equilibrium
This project will quantify gut oxygen levels of mice exposed to different partial pressures to provide a comprehensive evaluation of oxidative stress on the gut microbiome, its impact on bacterial community structure, and its relationship to the development of the “dysbiotic” microbiome associated with inflammatory bowel disease.