M.D., SUNY Downstate Medical School
Internship and Residency Training
Internal Medicine, UMDNJ-Rutgers Medical School
Postdoctoral Fellow and Assistant Research Scientist (NIH Physician-Scientist Award), Cell Biology and Environmental Medicine, NYU School of Medicine
American Board of Internal Medicine (1986)
Attending Physician, Bellevue Hospital Center Comprehensive Medical Clinic (1991-2004).
Attending Physician, NYU/Tisch Hospital, NY, NY (1997-2004)
Current Academic Positions
Associate Professor, SUNY Stony Brook School of Medicine (2010- )
Adjunct Assistant Professor, NYU School of Medicine (2005- )
NIH Physician Scientist Award, “Structure-function Relationships in the P450 Enzyme Family” 1986-1991
American Medical Association Physician’s Recognition Award with Special Commendation for Self-directed Learning, 1993-2000
Lupus Foundation Award, 1998-2000
NYU School of Medicine Award for Excellence in Teaching of Medical Students, 1999-2000
Arthritis Foundation NY Chapter, Young Scholar Award, “Immunological Mechanisms in Premature Atherosclerosis” 2000-2003
Outstanding Research by a Junior Faculty Member, NYU Department of Medicine Research Day, 2003
American Heart Association, Heritage Affiliate, Grant-in-Aid, “Immune Reactants, Cholesterol and Atherosclerosis” 2003-2004
NIH/National Heart, Lung and Blood Institute R01 “Immune Reactants, Cholesterol and Atherosclerosis” 2004-2008
Principal Investigator, Neurosciences Education and Research Foundation grant “Cholesterol Transport in Alzheimer’s: Role of Adenosine” 2004-2010
Elected, National Council, American Federation for Medical Research, 2007-2011
Arthritis Foundation, National, Innovative Research Award “Atherosclerosis in RA and Lupus: Restoring Cholesterol Balance” 2008-2011
Winthrop Research Institute Award “Impact of Anti-inflammatory Agents on Cholesterol Metablic Signature in Hu
Description of Research Interests/Activities
The overall objectives of the research program headed by Allison B. Reiss, M.D., are threefold: (1) To understand the mechanisms underlying the increased risk for developing cardiovascular disease seen in persons with the autoimmune disorders rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE, lupus). (2) To understand why pain-relieving medications that work through cyclo-oxygenase (COX) inhibition elevate the risk of cardiovascular events including myocardial infarction and stroke. This class of drugs, which includes specific inhibitors of COX-2 as well as non-steroidal anti-inflammatory medications, is widely used across the United States and around the world. Two members of the COX-2 group, rofecoxib and valdecoxib, were withdrawn from the market starting in 2004. (3) To develop therapeutic strategies to prevent and treat the accelerated atherosclerosis that occurs in rheumatic diseases and with prolonged use of COX inhibitors.
Working with co-investigator Dr. Steven Carsons, Chief of the Division of Rheumatology, Allergy and Immunology, we have studied disruption of cholesterol balance in the arterial wall by immune reactants and COX inhibitors and the consequent acceleration of the atherosclerotic process. Our laboratory is interested in the molecular mechanisms involved in the signaling pathways that modulate cholesterol homeostatic protein expression and in the physiologic effect of changes in cholesterol balance on the propensity of macrophages to adhere to the arterial wall and to form foam cells.
Atherosclerosis is increasingly recognized as a complex inflammatory disease. Immune reactants may influence critical metabolic events in the arterial wall by modulating expression of cholesterol transport proteins, including cholesterol 27-hydroxylase, an enzyme that provides one of the first lines of defense in the prevention of atherosclerosis. The 27-hydroxylase enzyme, which we have shown to be highly expressed in arterial endothelium and monocytes, catalyzes the first step in extrahepatic cholesterol metabolism and generates oxysterol signaling molecules (27-hydroxycholesterol) critical for expression of ATP-binding cassette transporter A1 (ABCA1), a molecule involved in cholesterol efflux from macrophages and which is defective in Tangier Disease (premature atherosclerosis with normal serum lipids). Cholesterol 27-hydroxylase and ABCA1 are key enzymes in elimination of cholesterol from macrophages and constitute a protective mechanism against atheroma formation.
We have shown that stimulation of human arterial endothelial cells and monocytoid cells in culture with immune complexes or the cytokine interferon (IFN)-gamma (both present at elevated levels in the circulation of SLE patients) markedly decreases expression of 27-hydroxylase and ABCA1. This downregulation of genes critical for export of cholesterol impedes cholesterol purging and leads to enhanced macrophage foam cell formation. In collaboration with the Rheumatology Faculty at WUH, we have confirmed the pro-atherogenic nature of plasma from persons with SLE by showing that incubation of cultured human monocytes/macrophages with SLE plasma suppresses expression of cholesterol 27-hydroxylase while enhancing expression of the scavenger receptor CD36 which is responsible for oxidized cholesterol uptake by the cell. Exposure of these macrophages to lupus plasma causes a dramatic increase in foam cell transformation upon treatment with modified low density lipoprotein cholesterol that is not seen when the cells are exposed to healthy control plasma. This line of research can lead to identification of susceptibility factors and potential disease markers of atherosclerotic risk in rheumatic diseases.
Similarly, we have found that COX inhibitors subdue expression of 27-hydroxylase and ABCA1 while augmenting CD36, leading to macrophage foam cell transformation. We are enrolling patients in a study examining the effect of administration of COX inhibiting medications on the cholesterol transport properties of their plasma and white blood cells.
We have found that methotrexate, an anti-inflammatory agent used to treat RA and known to reduce cardiovascular disease risk in RA patients, can bring up 27-hydroxylase and ABCA1 expression by activating the adenosine A2A receptor. We have applied multiple compounds that are able to activate the adenosine A2A receptor and have found them to be effective in stimulating 27-hydroxylase and ABCA1 and preventing foam cell formation, even in the presence of COX inhibitors, IFN-gamma, or lupus plasma. These adenosine A2A receptor ligands provide a new platform for therapeutic manipulations of cholesterol transport pathways. They have a much narrower activity than methotrexate and might therefore have a better side effect profile. A2A receptor agonists may have clinical application in reducing cardiovascular risk in vulnerable populations and we are exploring their potential use to improve the safety profile of COX inhibitors.
Alzheimer’s Disease (AD)
Emerging evidence supports a key role for cholesterol flux in the pathogenesis of AD. The focus of this aspect of the work is to elucidate the role of cholesterol metabolism on processing of amyloid precursor protein and consequent effects on production of amyloid beta, which may directly impact AD risk. Adenosine agonists may be useful in mitigating harmful effects of abnormal cholesterol metabolism on neurons. An understanding of the underlying pathology of AD may lead to the development of new and efficacious treatments.
Areas of Experience
Rheumatology, Allergy & Immunology
Research Team Members
Iryna Voloshyna, Ph.D. Michael J. Littlefield, B.A.
Representative Publications (selected, since 2004)
1. Reiss, A.B., Rahman, M.M., Chan, E.S.L., Montesinos, M.C., Awadallah, N.W., and Cronstein, B.N. Adenosine A2A Receptor Occupancy Stimulates Expression of Proteins Involved in Reverse Cholesterol Transport and Inhibits Foam Cell Formation in Macrophages. J. Leukocyte Biology. 2004, 76(3):727-734.
2. Reiss A.B., Patel C.A., Rahman M.M., Chan E.S., Hasneen K., Montesinos M.C., Trachman J.D., and Cronstein B.N. Interferon-gamma impedes reverse cholesterol transport and promotes foam cell transformation in THP-1 human monocytes/macrophages. Med. Sci. Monit. 2004; 10(11):BR420-425.
3. Reiss, A.B. and Glass, A.D. Atherosclerosis: immune and inflammatory aspects. J. Invest. Med. 2006; 54:123-131.
4. Chan, E.S.L., Fernandez, P., Merchant, A.A., Montecinos, M.C., Trzaska, S., Desai, A., Tung, C.F., Khoa, N.D., Pillinger, M.H., Reiss, A.B., Tomic-Canic, M., Chen, J.F., Schwarzschild, M.A., and Cronstein, B.N. Adenosine A2A receptors in diffuse dermal fibrosis. Arthritis Rheum. 2006; 54(8): 2632-2642.
5. Reiss, A.B., and Vagell, M.E. PPARgamma activity in the vessel wall: anti-atherogenic properties. Current Medicinal Chemistry. 2006; 13(26)3227-3238.
6. Reiss, A.B., and Edelman, S.D. Recent Insights into the Role of Prostanoids in Atherosclerotic Vascular Disease. Current Vascular Pharmacology. 2006; 4(4):395-408.
7. Chan, E.S.L., Zhang, H., Fernandez, P., Edelman, S.D., Pillinger, M.H., Ragolia, L., Palaia, T., Carsons, S.E., and Reiss, A.B. Effect of COX Inhibition on Cholesterol Efflux Proteins and Atheromatous Foam Cell Transformation in THP-1 Human Macrophages: A Possible Mechanism for Increased Cardiovascular Risk. Arthritis Res. Ther. 2007; 9(1):R4.
8. Reiss, A.B., Carsons, S.E., Rao, S., Edelman, S.D., Zhang, H., Fernandez, P., Cronstein, B.N., and Chan, E.S.L. Atheroprotective Effects of Methotrexate on Reverse Cholesterol Transport Proteins and Foam Cell Transformation in THP-1 Human Monocytes/Macrophages. Arthritis Rheum. 2008; 58(12):3675-3683.
9. Reiss, A.B., Wirkowski, E. Statins in neurological disorders: mechanisms and therapeutic value. ScientificWorldJournal. 2009; 9:1242-1259.
10. Reiss, A.B., Wan, D.W., Anwar, K., Merrill, J.T., Wirkowski, P.A., Shah, N., Cronstein, B.N, Chan, E.S., and Carsons, S.E. Enhanced CD36 scavenger receptor expression in THP-1 human monocytes in the presence of lupus plasma: linking autoimmunity and atherosclerosis. Exp. Biol. Med. 2009; 234(3):354-360.
11. Reiss AB, Anwar F, Chan ESL, and Anwar K. Disruption of cholesterol efflux by coxib medications and inflammatory processes: link to increased cardiovascular risk. J. Invest. Med. 2009; 57(6):695-702.
12. Reiss, A.B. Effects of inflammation on cholesterol metabolism: impact on lupus. Curr. Rheumatol. Rep. 2009; 11(4):255-260.
13. Reiss, A.B., Anwar, K., and Wirkowski, P. Lectin-like oxidized low density lipoprotein receptor 1 (LOX-1) in atherogenesis: a brief review. Curr. Med. Chem. 2009; 16(21):2641-2652.
14. Bingham TC, Cronstein BN, Fisher EA, Parathath S, Reiss A, Chan E. A2A adenosine receptor stimulation decreases foam cell formation by enhancing ABCA1-dependent cholesterol efflux. J. Leukoc. Biol. 2010; 87(4): 683-690.
15. Reiss, A.B., Anwar, K., Merrill, J.T., Chan, E.S., Awadallah, N.W., Cronstein, B.N., Michael Belmont, H., Belilos, E., Rosenblum, G., Belostocki, K., Bonetti, L., Hasneen, K., and Carsons, S.E. Plasma from systemic lupus patients compromises cholesterol homeostasis: a potential mechanism linking autoimmunity to atherosclerotic cardiovascular disease. Rheumatol. Int. 2010; 30(5):591-598.
TEACHING- Research Elective
The Reiss lab offers a research elective that is project-based, collaborative and tailored to the knowledge, skills and experience of the student (who may be an undergraduate, medical student, house officer or fellow). An initial overview of the laboratory’s research focus and of some of the relevant research literature in inflammation and atherosclerosis is provided. In addition, for those lacking substantial hands-on experience, an intensive tutorial in the techniques of cell culture, PCR and Western blotting is given. Students typically meet with Dr. Reiss several times each week to discuss concepts and ideas and, ultimately, to develop a significant, targeted research topic. This includes step-by-step protocol design as well as a thorough discussion of the potential challenges to data collection, reduction and analysis. The participant performs the study with close oversight and keeps meticulous records of the process. In many cases this experience has resulted in conference submission and/or publication in peer-reviewed journals. At the conclusion of the elective rotation period a faculty evaluation of the student’s performance is submitted.