Alan Friedman
| Title | Assistant Professor |
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| Institution | School of Medicine and Dentistry |
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| Department | Environmental Medicine |
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| Address | University of Rochester Medical Center
School of Medicine and Dentistry
601 Elmwood Ave, Box EHSC
Rochester NY 14642
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| University Regents Fellowship | University of California at Santa Barbara, CA | | 1980 |
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| American Chemical Society Summer Fellowship | San Diego State University, CA | | 1986 |
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| Chancellors Patent Fund Grant | University of California at Santa Barbara | | 1988 |
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| 1989 | Postdoctoral Reseach Fellowship | National institute of Health/National Cancer Institute | | 1990 |
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| 1991 | Research Fellowship | National Institute of Health/National Cancer Institute | | 1991 |
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| Distinguished Service Award | Eastman Kodak Company | | 1993 |
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| Distinguished Service Award | Eastman Kodak Company | | 1998 |
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| 2000 | European Consortium on Peroxidases | Johnson and JOhnson Clinical Diagnostics | | 2010 |
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| Provost's Multidisciplinary Award | University of Rochester | | 2012 |
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| Reach Funding Undergraduate Research (Micheal Nevid) University of Rochester |
The evaluation of biomarkers as diagnostic indicators for disease progression is an endeavor of intense academic and clinical research. Our group is interested in the regulation of cancer progression, which we are studying through a novel in vitro cell model system. This model, called the Prostatic Human Epithelial Cancer (PHEC) system, represents all three states of human prostate cancer progression: non-tumorigenic, tumorigenic and metastatic cells. For each state, we have individual cell lines in culture, and thus we are able to compare the three states directly, as they are generated from the same progenitor line. This allows us to study changes in expressed protein identities, concentrations, biomolecular interaction partners, and even genetic expression profiles, to understand the sub-cellular basis for prostate cancer progression.
Our research focuses on the identification of aberrant proteins and subtle changes in concentration in response to cellular changes, using mass spectrometry and other cutting edge protein chemistry tools. With these tools, we recently defined the behavior of one such protein, nucleoside diphosphate kinase A, or non-metastatic 23 H1 form (NM23-H1). Doing a comparative analysis of this protein in our PHEC cell lines, we discovered that NM23-H1 has a consistent regression in tumorigenic and metastatic states of cancer compared to its levels in the non-tumorigenic state, as illustrated by immunochemistry in Figure 1. This protein is the only known human histidine kinase, and may serve as the entry point for a two-component signal transduction (2CST), a style of protein regulation that is common in prokaryotes but seldom seen in eukaryotes above yeast. 2CST systems rely upon a histidine kinase for autophosphorylation, followed by the transfer of the phosphate group to a response regulator (RR), usually on an aspartic acid residue. The proposal of the role of NM23-H1 in such a 2CST system is outlined in Scheme 1. This is a new paradigm for the regulation of proteins in humans, and our laboratory is working to provide further evidence for the existence of the 2CST system in humans and to characterize its role in the progression of prostate cancer and its metastasis outside the prostate.
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Macgilvray ME, Lapek JD, Friedman AE, Quivey RG. Cardiolipin biosynthesis in Streptococcus mutans is regulated in response to external pH. Microbiology. 2012 Aug; 158(Pt 8):2133-43.
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Jaffré F, Friedman AE, Hu Z, Mackman N, Blaxall BC. ß-Adrenergic Receptor Stimulation Transactivates Protease-Activated Receptor 1 via Matrix Metalloproteinase 13 in Cardiac Cells. Circulation. 2012 Jun 19; 125(24):2993-3003.
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Deane R, Singh I, Sagare AP, Bell RD, Ross NT, Larue B, Love R, Perry S, Paquette N, Deane RJ, Thiyagarajan M, Zarcone T, Fritz G, Friedman AE, Miller BL, Zlokovic BV. A multimodal RAGE-specific inhibitor reduces amyloid ß-mediated brain disorder in a mouse model of Alzheimer disease. J Clin Invest. 2012 Apr 2; 122(4):1377-92.
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Lapek JD, McGrath JL, Ricke WA, Friedman AE. LC/LC-MS/MS of an innovative prostate human epithelial cancer (PHEC) in vitro model system. J Chromatogr B Analyt Technol Biomed Life Sci. 2012 Apr 15; 893-894:34-42.
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Sundar IK, Chung S, Hwang JW, Lapek JD, Bulger M, Friedman AE, Yao H, Davie JR, Rahman I. Mitogen- and Stress-Activated Kinase 1 (MSK1) Regulates Cigarette Smoke-Induced Histone Modifications on NF-?B-dependent Genes. PLoS One. 2012; 7(2):e31378.
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Mattiacio J, Walter S, Brewer M, Domm W, Friedman AE, Dewhurst S. Dense display of HIV-1 envelope spikes on the lambda phage scaffold does not result in the generation of improved antibody responses to HIV-1 Env. Vaccine. 2011 Mar 21; 29(14):2637-47.
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Lapek JD, Tombline G, Friedman AE. Mass spectrometry detection of histidine phosphorylation on NM23-H1. J Proteome Res. 2011 Feb 4; 10(2):751-5.
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Caito S, Rajendrasozhan S, Cook S, Chung S, Yao H, Friedman AE, Brookes PS, Rahman I. SIRT1 is a redox-sensitive deacetylase that is post-translationally modified by oxidants and carbonyl stress. FASEB J. 2010 Sep; 24(9):3145-59.
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McCloskey R, Menges C, Friedman A, Patel D, McCance DJ. Human papillomavirus type 16 E6/E7 upregulation of nucleophosmin is important for proliferation and inhibition of differentiation. J Virol. 2010 May; 84(10):5131-9.
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Block RC, Duff R, Lawrence P, Kakinami L, Brenna JT, Shearer GC, Meednu N, Mousa S, Friedman A, Harris WS, Larson M, Georas S. The effects of EPA, DHA, and aspirin ingestion on plasma lysophospholipids and autotaxin. Prostaglandins Leukot Essent Fatty Acids. 2010 Feb-Mar; 82(2-3):87-95.
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Nadtochiy SM, Burwell LS, Ingraham CA, Spencer CM, Friedman AE, Pinkert CA, Brookes PS. In vivo cardioprotection by S-nitroso-2-mercaptopropionyl glycine. J Mol Cell Cardiol. 2009 Jun; 46(6):960-8.
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Ehrenberg MS, Friedman AE, Finkelstein JN, Oberdörster G, McGrath JL. The influence of protein adsorption on nanoparticle association with cultured endothelial cells. Biomaterials. 2009 Feb; 30(4):603-10.
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Ryan EP, Bushnell TP, Friedman AE, Rahman I, Phipps RP. Cyclooxygenase-2 independent effects of cyclooxygenase-2 inhibitors on oxidative stress and intracellular glutathione content in normal and malignant human B-cells. Cancer Immunol Immunother. 2008 Mar; 57(3):347-58.
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Malkowski MG, Quartley E, Friedman AE, Babulski J, Kon Y, Wolfley J, Said M, Luft JR, Phizicky EM, DeTitta GT, Grayhack EJ. Blocking S-adenosylmethionine synthesis in yeast allows selenomethionine incorporation and multiwavelength anomalous dispersion phasing. Proc Natl Acad Sci U S A. 2007 Apr 17; 104(16):6678-83.
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Bell RD, Sagare AP, Friedman AE, Bedi GS, Holtzman DM, Deane R, Zlokovic BV. Transport pathways for clearance of human Alzheimer's amyloid beta-peptide and apolipoproteins E and J in the mouse central nervous system. J Cereb Blood Flow Metab. 2007 May; 27(5):909-18.
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Wang S, Friedman AE, Kool ET. Origins of high sequence selectivity: a stopped-flow kinetics study of DNA/RNA hybridization by duplex- and triplex-forming oligonucleotides. Biochemistry. 1995 Aug 1; 34(30):9774-84.
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Pandya KJ, Smith JL, Friedman A, Stilwell AM. Patterns of care of the elderly with cancer at a community hospital. Prog Clin Biol Res. 1990; 339:431-9.
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