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Frederick Coffman, PhD

Dr. Frederick Coffman is an Associate Professor in the Department of Health Informatics in the School of Health Professions on the Rutgers Biomedical and Health Science campus. He has served as the Associate Director of the Center for Biophysical Pathology at Rutgers New Jersey Medical School, and was previously in the Departments of Pathology at Rutgers New Jersey Medical School and Hahnemann University Medical School. He has performed basic and applied research in the areas of cancer and immunology; his areas of focus include the synergistic enhancement of TNF-mediated tumor cell killing by specific classes of DNA topoisomerase II inhibitors, the function of the chitinase family protein YKL-40 as a tumor cell survival factor, the regulation of DNA replication initiation in leukemia cells, and most recently disease-related informatics projects and laboratory-based investigations into differences in the biophysical properties of low grade and highly malignant cancer cells.

Research into the biophysical profiling of tumor cells is based on the observation that a small number of common phenotypes are shared among tumor cells, including the ability to invade and metastasize, despite the enormous complexity and variability of the genetic alterations in these cells. The ability to invade and metastasize necessarily involves physical characteristics of the cells that allow it to interact with other cells and matrix structures. We hypothesize that profiling the biophysical properties of these cells, using multiple approaches and examining both intrinsic characteristics and changes in biophysical parameters in response to external stimuli, will provide both useful information about basic cancer biology and for some cancers may be predictive of clinical behavior. We have utilized measurements of cellular impedance as well as dynamic mass rearrangements near the cell membrane to construct unique biophysical profiles of various cancer and noncancerous cell lines, and found that cancer cells with greater invasive and metastatic potential generally had significantly less dynamic mass rearrangement at the membrane than cells with low invasive and metastatic potential. We have also utilized laser Raman microspectrophotometry to map molecular distributions within cells, and discovered a unique halo of very highly ordered lipid molecules which remained associated with chromatin throughout the cell cycle, even during mitosis. This study was performed in collaboration with Dr. Bhagavathy Ramamurthy, who is an SHP faculty member in the Department of Physician Assistant Studies and Practice.  A collaboration has been very recently initiated with Dr. Ramamurthy and Dr. Gary Heir of NJDS in which laser Raman spectrophotometry is being used to map drug distributions in isolated neurons.

Frederick Coffman

Associate Professor

coffmafd@shp.rutgers.edu

B.S. Chemistry: Department of Chemistry, California State University, Long Beach

Ph.D. Biochemistry: Department of Biochemistry, University of California Riverside

Postgraduate Research Fellowship in Cellular and Molecular Endocrinology: Division of Biomedical Sciences, University of California Riverside

A. Refereed Original Articles
• Spindler, S.R., Siebert, P., Coffman, F.D. and Jurnak, F.J. The isolation of biologically active mRNA. Biochemical Education 12: 22-25, 1984.
• Coffman, F.D. and M.F. Dunn “Insulin – metal interactions. The binding of divalent cations to insulin hexamers and tetramers, and the assembly of insulin hexamers”. Biochemistry 27: 6179-6187, 1988.
• Coffman, F.D., L.M. Green, A. Godwin, and C.F. Ware. “Cytotoxicity mediated by tumor necrosis factor in variant subclones of the ME-180 cervical carcinoma line: modulation by specific inhibitors of DNA topoisomerase II.” J. Cell. Biochem. 39: 95-105, 1988
• Coffman, F.D., L.M. Green and C.F. Ware. “The relationship of receptor occupancy to the kinetics of cell death mediated by tumor necrosis factor” Lymphokine Res. 7: 371-383, 1988.
• Coffman, F. D., D. L. Haviland, and C. F.Ware. “Cytotoxicity by tumor necrosis factor is linked with the cell cyle but does not require DNA synthesis” Growth Factors 1: 357-364, 1989.
• Hameed, M., F. D. Coffman, S. Cohen and K. L. Fresa.”Differences in the pattern of proliferative responses with age in thymocytes undergoing spontaneous and induced proliferation.” Cellular Immunology 123: 405-416, 1989.
• Autieri, M. V., K. L. Fresa, F.D. Coffman, M.E. Katz and S. Cohen. “Induction of a cytoplasmic mediator of DNA synthesis in lymphocytes is mediated through a membrane-associated protein kinase.” Cell Regulation 1: 1015-1025, 1990.
• Baloch, Z., S. Cohen and F. D. Coffman. “Synergistic interactions between tumor necrosis factor and inhibitors of DNA topoisomerase I and II” J. Immunol. 145: 2908-2913, 1990.
• Coffman, F. D., K. L. Fresa and S. Cohen. “The initiation of lymphocyte DNA synthesis” J. Cell. Biochem. 45: 15-21, 1990.
• Coffman, F. D., K. L. Fresa, I.A. Oglesby and S. Cohen. “Control of DNA replication in a transformed lymphoid cell line: coexistence of activator and inhibitor activities”. Cellular Immunology 145: 381-389, 1991.
• Bereta, J., M. Bereta, F. D. Coffman, S. Cohen, and M. C. Cohen. “Inhibition of basal and TNF-enhanced binding of murine tumor cells to murine endothelium by transforming growth factor-ß.” J. Immunol. 148: 2932-2939, 1992.
• Fresa, K. L., M. V. Autieri, F. D. Coffman, I. Georgoff, and S. Cohen. “A cytosolic activator of DNA replication is tyrosine phosphorylated in its active form.” Exp. Cell Res. 205: 302-310, 1993.
• Coffman, F. D., K. L. Fresa, M. Hameed, and S. Cohen. “Characteristics of DNA replication in isolated nuclei initiated by an aprotinin binding protein.” J. Cell. Biochem. 51: 157-164, 1993.
• Coffman, F. D., I. Georgoff, K. L. Fresa, J. Sylvester, I. Gonzalez, and S. Cohen. “In vitro replication of plasmids containing human ribosomal gene sequences: origin localization and dependence on an aprotinin-binding cytosolic protein.” Exp. Cell Res. 209: 123-132, 1993.
• Ye, X., I. Georgoff, S. Fleisher, F. D. Coffman, S. Cohen, and K. L. Fresa. “The mechanism of epipodophyllotoxin-induced thymocyte apoptosis: possible role of a novel Ca2+-independent protein kinase.” Cellular Immunol. 151: 320-335, 1993.
• Yang, G., F. D. Coffman, and E. F. Wheelock. “Characterization and purification of a macrophage triggering factor produced in mycoplasma arginini-infected L5178Y cell cultures.” J. Immunol. 153: 2579-2591, 1994.
• Bereta, M., J. Bereta, I. Georgoff, F. D. Coffman, S. Cohen and M. C. Cohen “Methylxanthines and calcium-mobilizing agents inhibit the expression of cytokine-inducible nitric oxide synthase and vascular cell adhesion molecule-1 in murine microvascular endothelial cells.” Exp. Cell Res. 212: 230-242, 1994.
• Baloch, Z., S. Cohen, K. Fresa, and F.D. Coffman “Modulation of topoisomerase activities by tumor necrosis factor.” Cell. Immunol. 160: 98-103, 1995.
• Townsend, R. M., J. L. Dzuris, I Mizra, T. Sieck, F. D. Coffman and K. J. Blank. “Inhibition of T cell activation by an autoantibody indiced by murine retrovirus infection.” Clin. Immunol. Immunopathol. 82: 263-273, 1997.
• Wang, Q., Luo, X., Kheir, A., Coffman, F. D., and Studzinski, G. P. “Retinoblastoma protein-overexpressing HL60 cells resistant to 1,25-dihydroxyvitamin D3 display increased CDK2 and CDK6 activity and shortened G1 phase.” Oncogene 16: 2729-2737, 1998.
• Ye X. Mody NS. Hingley ST. Coffman FD. Cohen S. Fresa KL. “Protein phosphorylation associated with epipodophyllotoxin-induced apoptosis of lymphoid cells: role of a serine/threonine protein kinase.” Clin. Immunol. Immunopath. 89(2):117-25, 1998.
• Wang, Q., Studzinski, G.P., Chen, F., Coffman, F.D. and Harrison, L. E. “p53/56lyn antisense shifts the 1,25 dihydroxyvitamin D3-induced G1/S Block in HL60 cells to S phase. J. Cell. Physiol. 183: 238-246, 2000.
• De la Fuente, C., Santiago, F., Chong, S.Y., Deng, L., Mayhood, T., Fu, P., Stein, D., Denny, T., Coffman, F., Azimi, N., Mahieux, R. and Kashanchi, F. “Overexpression of p21waf1 in HTLV-I_infected cells and its association with cyclin A/cdk2.” J. Virol. 74:7270-7283, 2000.
• Chong, S. Y., Zhang, M., Lin, Y.-C., Coffman, F., Garcia, Z., Ponzio, N. and Raveche, E.S. “The growth regulatory effects of B-cell-specific-activator-protein (BSAP) in NZB malignant B-1 cells.” Cancer Immunology Immunotherapy 50 (1): 41-50, 2001.
• Chong S. Y., Lin, Y-C., Czarneski, J., Zhang, M., Coffman, F., Kashanchi, F., and Raveche E. “Cell cycle effects of IL-10 on malignant B-1 cells.” Genes & Immunity. 2(5):239-47, 2001.
• de la Fuente C. Wang L. Wang D. Deng L. Wu K. Li H. Stein LD. Denny T. Coffman F. Kehn K. Baylor S. Maddukuri A. Pumfery A. Kashanchi F. “Paradoxical effects of a stress signal on pro- and anti-apoptotic machinery in HTLV-1 Tax expressing cells.” Mol. Cell. Biochem. 245(1-2):99-113, 2003.
• Coffman, F.D., He, M., Diaz, M.-L. and Cohen, S. “DNA replication initiates at different sites in early and late S phase within human ribosomal RNA genes.” Cell Cycle 4(9): 1223-1226, 2005.
• Hameed, M.R., Lin, T-Z, Coffman, F.D. Cohen, M.C., Fernandes, H., Aviv, H., Benevenia,J., Aisner, S.C. and Cohen, S. “Gene expression analysis of a Dedifferentiated Liposarcoma- Differences between high and low grade areas . Analysis of two cases and literature review.” Journal of Musculoskeletal Research 9(1): 9-20, 2005.
• Hameed, M.R., Lin, T-Z, Coffman, F.D. Cohen, M.C., Fernandes, H., Benevenia,J., Patterson, F., Aisner, S.C. and Cohen, S. “Molecular markers in osteosarcoma – a cDNA microarray and RT-PCR analysis.” Journal of Musculoskeletal Research 9(2): 77-84, 2005.
• Coffman, F.D., He, M., Diaz, M.-L. and Cohen, S. “Multiple initiation sites within the human ribosomal RNA gene.” Cell Cycle 5(11): 1223-33 2006.
• Kim, S.H., Das, K., Noreen, S., Coffman, F. and Hameed, M. Prognostic implications of immunohistochemically detected YKL-40 expression in breast cancer. World Journal of Surgical Oncology 5:17 (2007).
• Scaglione, B., Salerno, E., Balan, M., Coffman, F., Landgraf, P., Abbasi, F., Kotenko, S., Marti, G. and Raveche E.S. (2007). Murine models of CLL: role of microRNA-16 in the NZB mouse model. Brit. J. Haematol 139: 645-657.
• Salerno, E., Scaglione, B.J., Coffman, F.D., Brown, B.D., Baccarini, A., Fernandes, H., Marti, G. and Raveche, E.S. (2009). Correcting miR-15a/16 genetic defect in New Zealand Black mouse model of CLL enhances drug sensitivity. Mol. Cancer Ther. 8(9): 2684 – 2692.
• He, M., Shah, D, Choung, H.Y.G. and Coffman, F.D. (2009). The splicing factor SF2/ASF binds to ARS homologues in a human rDNA replication origin. Cell Cycle 8:2631-42.
• Coffman F, Hamid R, Cohen MC, Garippa R, Cohen S. (2011). Biophysical profiling of tumor cell lines. Anal. Cell. Pathol. 34:225-234.
• Coffman F.D., Reyes M-L, Brown M, Lambert WC, and Cohen S. (2011) Localization of ORC1 during the cell cycle in human leukemia cells. Anal. Cell. Pathol. 34: 355-361.
• Hoover DJ, Zhu V, Chen R, Briley K, Rameshwar P, Cohen S, Coffman FD (2013). Chitinase Family Glycoprotein YKL-40 Expression in the Differentiation of Human Mesenchymal Stem Cells Towards Bone, Cartilage, and Neuronal Phenotypes. Differentiation PLoS ONE 8(5): e62491. doi:10.1371/journal.pone.0062491.
• Zhang P, Herbig U, Coffman F, Lambert M (2013). Nonerythroid alpha spectrin prevents telomere dysfunction after DNA interstrand cross-link damage. Nuc. Acids Res. 41: 5321-5340.
• DiCosmo-Ponticello CJ, Coffman FD, Cohen S, Cohen MC (2014). MIF inhibits monocytic movement through a non-canonical receptor and disruption of temporal Rho GTPase activities in U-937 cells. Cytokine 69: 47-55.
• Ramamurthy B, Coffman FD, Cohen S (2015). A perspective on digital and computational pathology. J. Pathol. Inform. 6:29.
• Lau K. Coffman F, Ramamurthy B (2015). Portrait of a dying cell. The Pathologist 14, 1115.
• Ziarek J, Kleist A, London N, Raveh B, Malik R, Montpas N, Bonneterre J, St-Onge G, Kremer KN, DiCosmo-Ponticello C, Koplonski CA, Roy I, Stephens BS, Thelen S, Veldkamp CT, Coffman FD, Cohen MC, Dwinell MB, Thelen M, Hedin KE, Peterson FC, Marchese A, Heveker N, Volkman BF (2017) Structural basis of CXCR4 recognition by a constitutively monomeric CXCL12 and implications for receptor activation. Sci Signal 10: eaah5756.
• Ramamurthy B, Cohen S, Canales M, and Coffman FD. (2018). Three-dimensional cellular Raman analysis: evidence of highly ordered lipids within cell nuclei. Journal of Histochemistry & Cytochemistry. 66(12):889-902, 2018 Dec.
• Pastore RL, Murray JA, Coffman FD, Mitrofanova A, Srinivasan S. (2019) Physician review of a celiac disease risk estimation and decision-making expert system. Journal of the American College of Nutrition. 1-7.

B. Books, Monographs and Chapters
• Ware, C.F., F. Coffman, L.M. Green and W. F. Fletcher (1988) “Hierarchy of molecular mechanisms controlling the sensitivity of tumor cells to cytolysis by lymphotoxin and tumor necrosis factor” in “Tumor Necrosis Factor/Cachectin and Related Cytokines”, B. Bonavida, G.E. Gifford, H. Kirchner and L.J.Old eds. S. Karger AG (Basel), pp. 26-31.
• Coffman, F.D., K. Fresa, and S. Cohen (1989). “Intracellular regulation of proliferation in normal and neoplastic lymphoid cells.” In “New Horizons of Tumor Immunotherapy” M. Torisu and T. Yoshida editors, Elsevier Science Publishers B.V., pp 3-16.
• Studzinski, George P and Coffman, Frederick D (December 2007) Somatic and Stem Cell Differentiation in vitro: Model Systems. In: ENCYCLOPEDIA OF LIFE SCIENCES. John Wiley & Sons, Ltd: Chichester http://www.els.net/ [10.1002/9780470015902.a0002565.pub2] • Danilenko, M, Coffman, FD, Studzinski, GP (2012). Differentiation of Somatic Cells, Stem Cells, and Stem Cell Variants: In Vitro Models. In: ENCYCLOPEDIA OF LIFE SCIENCES. John Wiley & Sons, Ltd: Chichester. DOI: 10.1002/9780470015902.a0002565.pub3
• Coffman FD, Cohen S (2013). Impedance measurements in the biomedical sciences. In: Modern Trends in Imaging: Pathology at a Crossroads. 185: pp185-206.
• Studzinski GP, Gocek E, Coffman F, Danilenko M (2017). Effects of vitamin D derivatives on differentiation, cell cycle and apoptosis in hematological malignancies. Chapter 94, Vitamin D, 4th Edition, Volume 2: Health, Disease and Therapeutics; David Feldman Ed., Academic Press. eBook ISBN: 9780128099643; Hardcover ISBN: 9780128099636

C. Other Articles
• Coffman, F.D. and S. Cohen. (1989) “Aging and defective lymphoid cell activation. Experimental Gerontology 24: 437-449, 1989.
• Coffman, F.D. and Cohen, S. (1997) “Regulation of DNA replication initiation in mammalian lymphocyte systems.” Indian J. Biochem. Biophys. 34: 192-198.
• Coffman, F.D. and Studzinski, G.S. (1999) “Differentiation-related mechanisms which suppress DNA replication.” Exp. Cell Res. 248: 58-73.
• Coffman, F.D. (2008) “CHI3L1 – At the Interface of Proteomics and Glycomics”. Critical Reviews in Clinical Laboratory Science, 45:6, 531-562.
• Coffman, F.D. and Cohen, S. (2012) “Impedance measurements in the biomedical sciences.” Anal. Cell. Pathol. 35: 363-374.

The four attached photos are from our publication utilizing laser Raman microspectrophotometry to examine the distribution of macromolecules in human cancer cells. These images are of the human osteosarcoma cell line MG-63, and depict the distributions of two different lipid conformations, gauche and trans, as well as the distribution of the ratio of trans to gauche lipids, which indicates the location of the highest concentrations of highly ordered lipids in the cell.

MG-63 Light Microscope: light microscope image of the cell

MG-63 2850 Gauche lipids: distribution of the Raman peak at 2850 cm-1, which are lipids containing kinks in the fatty acid tails and thus pack more loosely (or less ordered)

MG-63 2870 Trans lipids: distribution of the Raman peaks at 2870 cm-1, which are lipids containing linear fatty acid tails and thus can pack together tightly (more ordered)

MG-63 2870/2850 lipid ratio: the ratio of the two lipid peaks, 2870 cm-1/2850 cm-1, is a well-documented measure of the locations of highest lipid order and tightest packing within the cell. As seen in this panel, and in others within the publication, the most highly ordered lipids are present throughout the nuclear interior and appear associated with nuclear chromatin (note: most of the lipids are not within the nucleus, as can be seen in the separate 2850 and 2870 images, but the most highly ordered lipid regions are in the nucleus).

The four attached photos are from our publication utilizing laser Raman microspectrophotometry to examine the distribution of macromolecules in human cancer cells. These images are of the human osteosarcoma cell line MG-63, and depict the distributions of two different lipid conformations, gauche and trans, as well as the distribution of the ratio of trans to gauche lipids, which indicates the location of the highest concentrations of highly ordered lipids in the cell.

MG-63 Light Microscope: light microscope image of the cell
MG-63 2850 Gauche lipids: distribution of the Raman peak at 2850 cm-1, which are lipids containing kinks in the fatty acid tails and thus pack more loosely (or less ordered)
MG-63 2870 Trans lipids: distribution of the Raman peaks at 2870 cm-1, which are lipids containing linear fatty acid tails and thus can pack together tightly (more ordered)
MG-63 2870/2850 lipid ratio: the ratio of the two lipid peaks, 2870 cm-1/2850 cm-1, is a well-documented measure of the locations of highest lipid order and tightest packing within the cell. As seen in this panel, and in others within the publication, the most highly ordered lipids are present throughout the nuclear interior and appear associated with nuclear chromatin (note: most of the lipids are not within the nucleus, as can be seen in the separate 2850 and 2870 images, but the most highly ordered lipid regions are in the nucleus).

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