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Faculty Detail     Name ROBERT W HARDY   Campus Address BMR2 536 Zip 2180 Phone 205-934-9925 E-mail rwfh1@uab.edu Other websites

Education Undergraduate  University of Waterloo, Canada    1975  BSc (Honors, Biology & Chemistry)  Graduate  University of Toronto, Canada    1988  PhD  Fellowship  Washington University    1990  Post Doctoral Fellowship in Clinical Chemistry and Diabetes Research

Certifications DABCC   1997

Faculty Appointment(s) Appointment Type Department Division Rank Primary  Pathology   Laboratory Medicine Professor Secondary  Cell, Developmntl, & Integrative Biology  Cell, Developmntl, & Integrative Biology Professor Center  Center for Aging  Center for Aging Professor Center  Center for Metabolic Bone Disease  Center for Metabolic Bone Disease Professor Center  Comprehensive Cancer Center  Comprehensive Cancer Center Professor Center  Medicine  Comprehensive Diabetes Ctr Professor

Graduate Biomedical Sciences Affiliations Cancer Biology  Dentistry  Integrative Biomedical Sciences  Medical Scientist Training Program  Molecular and Cellular Pathology Program  Optometry  Pathobiology and Molecular Medicine  Waiting to be Seated

Biographical Sketch  INSTITUTION AND LOCATION DEGREE YEAR(s) FIELD OF STUDY University of Waterloo, Canada BSc 1975 Biology & Chemistry University of Toronto, Canada MSc & PhD 1982 & 1988 Clinical Biochemistry Washington University, St. Louis, MO Post-doc 1988-90 Diabetes Univ. of Alabama at Birmingham, Birmingham, AL Post-doc 1990-91 Diabetes AWARDS/HONORS 1982 Open Masters Fellowship, University of Toronto 1984 Open Doctoral Fellowship, University of Toronto 1985 Mitchell Scholarship, Life Sciences Department, University of Toronto 1986 Med-Chem Award, Canadian Society of Clinical Chemists 1988-1990 Canadian Diabetes Association Individual Research, Post Doctoral Fellowship 1988-1991 Individual Research Postdoctoral Fellowship, Canadian Diabetes Association 1989 Young Investigator Award, Academy of Clinical Laboratory Physicians and Scientists 1999 Fellow of the National Academy of Clinical Biochemistry 2000 Editorial Board Laboratory Medicine 2008 Sr. Associate Editor for Laboratory Investigation

Society Memberships Organization Name Position Held Org Link AACC      ACLPS

Research/Clinical Interest Title Cancer cell metastasis. Description My primary area of interest is to understand how individual fatty acids affect disease processes at the cellular and molecular level. In particular I am interested in cancer cell metastasis. Cancer cell metastasis: The Ras superfamily of small GTPases control a wide range of cellular processes by switching between inactive GDP- and active GTP-bound states. These active proteins regulate cell behavior by binding to effector molecules and changing their location, activity and protein-protein interactions. Mutated versions of the Ras genes were first identified in human cancers over 20 years ago. The importance of aberrant Ras activation in oncogenesis is well established. Members of both the Ras and Rho subfamilies are known to affect cell proliferation. More recently it has been suggested that Ras and Rho signaling pathways crosstalk in such a way as to favor transformation and cell proliferation. Exactly how these two Ras superfamily members communicate is not entirely clear. One recent study indicated that in NIH 3T3 cells oncogenic Ras activates RhoA by inhibiting Ras induced p190Rho-GAP sequestration in a detergent resistant membrane (DRM) fraction. We have demonstrated that the long chain saturated fatty acid, stearate (C18:0), found in meat and chocolate, inhibits epidermal growth factor induced breast cancer cell proliferation. More recently we have show that this inhibition of cell proliferation is accompanied by an arrest of the cell cycle, an increase in Ras activity and a decrease in Rho activity. We are interested in persuing the mechanism whereby stearate stimulates Ras activity and yet inhibits Rho activity. In addition we are also interested in determining whether dietary stearate inhibits Ras mediated breast cancer tumor formation in vivo. The importance of these studies is that this is the first mechanistic evidence of a nutrient interfering with Ras-Rho crosstalk and may represent a novel dietary approach to inhibition of cancer progression. In addition we are also interested in determining whether dietary stearate inhibits Ras mediated breast cancer tumor formation in vivo. Specifically we have shown that dietary stearate reduces breast cancer incidence and tumor burden in a rat carcinogenesis model. It also reduces metastatic tumor burden and works synergistically with paclitaxel to reduce the incidence of metastasis in a nude mouse model of breast cancer metastasis. Ongoing studies include examining the effects of dietary stearate on fat distribution and how dietary stearate disrupts Ras-Rho crosstalk.

Selected Publications  Publication PUBMEDID Azrad M, Zhang K, Vollmer RT, Madden J, Polascik TJ, Snyder DC, Ruffin MT, Robertson CN, Moul JW, Brenner D, Hardy RW, Wendy Demark-Wahnefried W. Prostatic alpha-linolenic acid (ALA) is positively associated with aggressive prostate cancer: A relationship which may be modified by genetic variation in ALA metabolism PLoS One 2012;7:e53104.  23285256  Williams V, Martin R, Franklin JL, Hardy RW, Messina JL. Injury-Induced Insulin Resistance in Adipose Tissue. Biochemical and Biophysical Research Communications 2012;421:442-448.  22521887  Cowey S, Szafran AA, Kappes J, Zinn KR, Siegal GP, Desmond RA, Kim H, Evans L, Hardy RW. Breast cancer metastasis to bone: evaluation of bioluminescent imaging and microSPECT/CT for detecting bone metastasis in immunodeficient mice. Clin Exp Metastasis. 2007;24:389-401.   17541709  Cowey S, Hardy RW. The metabolic syndrome: a high risk state for cancer? Am J Pathol. 2006;169:1505-1522.   17071576  Zhao H, Hardy RW. Long chain saturated fatty acids induce annexin II translocation to detergent resistant membranes. Biochem J. 2004;381:463-469.  15099193  Li C, Zhao X, Toline EC, Siegal GP, Evans LM, Ibrahim-Hashim A, Desmond RA, Hardy RW. Prevention of carcinogenesis and inhibition of breast cancer tumor burden by dietary stearate. Carcinogenesis. 2011;32:1251–1258.  3149204  Evans LM, Toline EC, Desmond R, Siegal GP, Ibrahim-Hashim A, Hardy RW. Dietary stearate reduces breast cancer metastasis burden in athymic nude mice. Clin Exp Metastasis. 2009;26:415-424.   2946234  Evans LM, Cowey SL, Siegal GP, Hardy RW. Stearate preferentially induces apoptosis in human breast cancer cells. Nutr Cancer. 2009;61:746–753.   2946230  Byon CH, Hardy RW, Ren C, Ponnazhagan S, Welch DR, McDonald JM, Chen Y. Free fatty acids enhance breast cancer cell migration through plasminogen activator inhibitor-1 and SMAD4. Lab Invest. 2009;89:1221–1228.  2905319  Deng Z-b, Poliakov A, Clements R, Liu C, Liu Y, Wang J, Xiang X, Garvey T, Michalek S, Grizzle WE, Hardy RW, Mobley J, Zhang H-G. Adipose tissue exosome-like vesicles mediate activation of macrophage induced insulin resistance. Diabetes. 2009;58:2498–2505.  2768161  First Prev   1 2 of  2  Next Last

Keywords cancer, metastasis

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