Research Bio
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.
| Reach Funding Undergraduate Research (Micheal Nevid) University of Rochester |
2012 |
| Provost's Multidisciplinary Award | University of Rochester |
2010 |
| European Consortium on Peroxidases | Johnson and JOhnson Clinical Diagnostics |
1998 - 2000 |
| Distinguished Service Award | Eastman Kodak Company | Rochester, NY |
1993 |
| Distinguished Service Award | Eastman Kodak Company | Rochester, NY |
1991 |
| Research Fellowship | National Institute of Health/National Cancer Institute | California Institute of Technology, Pasadena, CA |
1990 - 1991 |
| Postdoctoral Reseach Fellowship | National institute of Health/National Cancer Institute | Columbia University, New York, NY |
1988 - 1989 |
| Chancellors Patent Fund Grant | University of California at Santa Barbara |
1986 |
| American Chemical Society Summer Fellowship | San Diego State University, CA |
1980 |
| University Regents Fellowship | University of California at Santa Barbara, CA | 1982, 1984, 1986 |
|
2015 Feb
Lapek JD, Tombline G, Kellersberger KA, Friedman MR, Friedman AE. "Evidence of histidine and aspartic acid phosphorylation in human prostate cancer cells." Naunyn-Schmiedeberg's archives of pharmacology. 2015 Feb; 388(2):161-73. Epub 2014 Nov 06. |
2014 Feb 7
Rahman I, Sundar IK, Nevid MZ, Friedman AE. "Cigarette smoke induces distinct histone modifications in lung cells: implications for the pathogenesis of COPD and lung cancer." Journal of proteome research. 2014 Feb 7; 13(2):982-96. Epub 2013 Dec 13. |
2013 Nov 1
Yao H, Hwang JW, Sundar IK, Friedman AE, McBurney MW, Guarente LP, Gu W, Kinnula VL, Rahman I. "SIRT1 redresses the imbalance of tissue inhibitor of matrix metalloproteinase-1 and matrix metalloproteinase-9 in the development of mouse emphysema and human COPD." American journal of physiology. Lung cellular and molecular physiology. 2013 Nov 1; 305(9):L615-24. Epub 2013 Sep 13. |
2013 Apr
Badding MA, Lapek JD, Friedman AE, Dean DA. "Proteomic and functional analyses of protein-DNA complexes during gene transfer." Molecular therapy : the journal of the American Society of Gene Therapy. 2013 Apr; 21(4):775-85. Epub 2012 Nov 20. |
2013
Tombline G, Schwingel JM, Lapek JD, Friedman AE, Darrah T, Maguire M, Van Alst NE, Filiatrault MJ, Iglewski BH. "Pseudomonas aeruginosa PA1006 is a persulfide-modified protein that is critical for molybdenum homeostasis." PloS one. 2013 8(2):e55593. Epub 2013 Feb 08. |
