Since 1993, David Sherr’s laboratory has conducted research on how common environmental pollutants, such as dioxins, polycyclic aromatic hydrocarbons and PCBs, adversely affect the growth and behavior of several different types of normal and malignant cells. In previous work, the Sherr laboratory studied how environmental chemicals affect the development of the immune system. In specific, his laboratory demonstrated that aromatic hydrocarbons (generated by the combuston of any carbon source) compromise the function of bone marrow cells required for the development of antibody-forming cells. These cells are critical for immune protection against viruses and bacteria. This work had its orignis in Dr. Sherr’s graduate studies on the ontogeny of lymphocyte development.
More recently, Dr. Sherr’s laboratory has focused on the molecular mechanisms that initiate and maintain breast cancer and on the effects of environmental chemicals on these processes. The laboratory has shown that a cellular protein receptor, referred to as the aryl hydrocarbon receptor (AhR), plays an important role in the initiation and progression of human breast cancer. The results explain, in part, the association between environmental chemical exposure and breast cancer risk. Perhaps most importantly, these studies demonstrate that the AhR drives human breast cancer cells to invade and, presumably, metastasize even in the absence of environmental chemicals. These observations have led to the development of AhR inhibitors which block AhR activity and prevent tumor cells from invading. One immediate goal of the laboratory, therefore, is the development of potent AhR inhibitors as novel, targeted therapeutics to be used for treatment of all breast cancers but especially for treatment of “triple negative” or chemotherapy-resistant breast cancers. Interestingly, preliminary studies suggest that these AhR inhibitors could be useful for treatment of several other cancer cell types.
A new area of study in Dr. Sherr’s laboratory is the analysis of the role of the AhR in blood cell development. These studies are important from both an environmental science and medical science point of view. Studies performed to date suggest that the AhR plays an important roll in the normal development of blood cells. The results suggest the intriguing possibility that common environmental pollutants can alter normal blood cell development by interfering with AhR signaling.
Dr. Sherr came to BUSPH from the faculty of Harvard Medical School, where he had earlier been a postdoctoral fellow in the department of Nobel Laureate Baruj Benacerraf. The Sherr Laboratory is funded by research grants from the National Institute of Environmental Health Sciences, the NIH Superfund Basic Research Program, and the Art BeCAUSE breast cancer foundation. Dr. Sherr is the Director of the Boston University Immunology Training Program, and a member of the Amyloid Treatment Research Program, the BU Cancer Center, the Hematology/Oncology Training Program, and the BU Hormone-dependent Cancer Center. He has trained 21 postdoctoral (M.D. or Ph.D.) and 11 predoctoral (M.D. and/or Ph.D.) fellows.
- Graduate Faculty (Primary Mentor of Grad Students), Boston University School of Medicine, Graduate Medical Sciences
- Professor, Pathology & Laboratory Medicine, Boston University School of Medicine
- Director, Superfund Research Program , Boston University
- Director, Immunology Training Program, Boston University
- Cornell University, PhD
- Brandeis University, BA
- Published on 4/8/2019
Takenaka MC, Gabriely G, Rothhammer V, Mascanfroni ID, Wheeler MA, Chao CC, Gutiérrez-Vázquez C, Kenison J, Tjon EC, Barroso A, Vandeventer T, de Lima KA, Rothweiler S, Mayo L, Ghannam S, Zandee S, Healy L, Sherr D, Farez MF, Pratt A, Antel J, Reardon DA, Zhang H, Robson SC, Getz G, Weiner HL, Quintana FJ. Control of tumor-associated macrophages and T cells in glioblastoma via AHR and CD39. Nat Neurosci. 2019 05; 22(5):729-740. PMID: 30962630.
- Published on 4/1/2019
Li A, Lu X, Natoli T, Bittker J, Sipes NS, Subramanian A, Auerbach S, Sherr DH, Monti S. The Carcinogenome Project: In Vitro Gene Expression Profiling of Chemical Perturbations to Predict Long-Term Carcinogenicity. Environ Health Perspect. 2019 Apr; 127(4):47002. PMID: 30964323.
- Published on 1/1/2019
Ash PEA, Dhawan U, Boudeau S, Lei S, Carlomagno Y, Knobel M, Al Mohanna LFA, Boomhower SR, Newland MC, Sherr DH, Wolozin B. Heavy Metal Neurotoxicants Induce ALS-Linked TDP-43 Pathology. Toxicol Sci. 2019 Jan 01; 167(1):105-115. PMID: 30371865.
- Published on 12/8/2018
Mohamed HT, Gadalla R, El-Husseiny N, Hassan H, Wang Z, Ibrahim SA, El-Shinawi M, Sherr DH, Mohamed MM. Inflammatory breast cancer: Activation of the aryl hydrocarbon receptor and its target CYP1B1 correlates closely with Wnt5a/b-ß-catenin signalling, the stem cell phenotype and disease progression. J Adv Res. 2019 Mar; 16:75-86. PMID: 30899591.
- Published on 11/15/2018
Esser C, Lawrence BP, Sherr DH, Perdew GH, Puga A, Barouki R, Coumoul X. Old Receptor, New Tricks-The Ever-Expanding Universe of Aryl Hydrocarbon Receptor Functions. Report from the 4th AHR Meeting, 29?31 August 2018 in Paris, France. Int J Mol Sci. 2018 Nov 15; 19(11). PMID: 30445691.
- Published on 5/7/2018
Narasimhan S, Stanford Zulick E, Novikov O, Parks AJ, Schlezinger JJ, Wang Z, Laroche F, Feng H, Mulas F, Monti S, Sherr DH. Towards Resolving the Pro- and Anti-Tumor Effects of the Aryl Hydrocarbon Receptor. Int J Mol Sci. 2018 May 07; 19(5). PMID: 29735912.
- Published on 4/24/2018
Krishnan S, Ding Y, Saedi N, Choi M, Sridharan GV, Sherr DH, Yarmush ML, Alaniz RC, Jayaraman A, Lee K. Gut Microbiota-Derived Tryptophan Metabolites Modulate Inflammatory Response in Hepatocytes and Macrophages. Cell Rep. 2018 Apr 24; 23(4):1099-1111. PMID: 29694888.
- Published on 4/1/2018
Leung A, Zulick E, Skvir N, Vanuytsel K, Morrison TA, Naing ZH, Wang Z, Dai Y, Chui DHK, Steinberg MH, Sherr DH, Murphy GJ. Notch and Aryl Hydrocarbon Receptor Signaling Impact Definitive Hematopoiesis from Human Pluripotent Stem Cells. Stem Cells. 2018 07; 36(7):1004-1019. PMID: 29569827.
- Published on 3/21/2018
Rothhammer V, Borucki DM, Kenison JE, Hewson P, Wang Z, Bakshi R, Sherr DH, Quintana FJ. Detection of aryl hydrocarbon receptor agonists in human samples. Sci Rep. 2018 Mar 21; 8(1):4970. PMID: 29563571.
- Published on 1/1/2018
Wang, Z, Novikov O, Stanford-Zulick EA, Kenison-White J., Sherr DH. National Academy of Sciences, The Promise of Genome Editing to Advance Environmental Health Research Workshop. Tracking an AHR Regulatory Circuit in Cancer with AHR Inhibitors and CRISPR/Cas9 Knockdown. Washington DC. 2018.
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