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Faculty Detail    
Name DOUGLAS R HURST
 
Campus Address VH G019 Zip 0019
Phone 205-934-2951
E-mail dhurst@uab.edu
Other websites
     


Faculty Appointment(s)
Appointment Type Department Division Rank
Primary  Pathology   Molecular & Cellular Pathology Assistant Professor
Center  Comprehensive Cancer Center  Comprehensive Cancer Center Assistant Professor

Graduate Biomedical Sciences Affiliations
Cancer Biology 
Cell, Molecular, & Developmental Biology 
Medical Scientist Training Program 
Pathobiology and Molecular Medicine 

Biographical Sketch 
Dr. Hurst received his BS degree from the College of Charleston and his PhD in Biochemistry from the Florida State University where he was a DoD Breast Cancer Research Fellow. He completed postdoc training in Cancer Biology with Danny Welch at the University of Alabama at Birmingham where he was a Ruth L. Kirschstein NIH fellow. He is currently an Assistant Professor in the Department of Pathology.

Society Memberships
Organization Name Position Held Org Link
American Association for Cancer Research  member  http://www.aacr.org/ 
American Association for the Advancement of Science  member  http://www.aaas.org/ 
American Society for Biochemistry and Molecular Biology  member  http://www.asbmb.org/ 
American Society for Matrix Biology  member  http://www.asmb.net/ 
Metastasis Research Society  member  http://www.metastasis-research.org/ 

Research/Clinical Interest
Title
Molecular mechanisms of cancer metastasis
Description
Metastasis is the major reason for morbidity and mortality of cancer patients. Therefore, understanding how to effectively target metastasis is vital in order to treat patients with this disease. The molecular mechanisms of metastasis are distinct from the mechanisms regulating growth of the primary tumor and every step of metastasis requires the coordinate expression of specific genetic programs. Several metastasis-associated genes are regulated epigenetically by SIN3:histone deacetylase (HDAC) chromatin remodeling complexes through the recruitment of protein and DNA modifying enzymes. The functional specificity (i.e., which genes they regulate and, as a result, the phenotype that is altered) of these complexes is dictated by their composition and resulting enzyme activity. Our lab focuses on the characterization of the composition and enzyme activity of SIN3:HDAC complexes that regulate chromatin remodeling events important for metastasis to enable the identification of potential targets and a restoration of non-metastatic SIN3:HDAC complexes.

Selected Publications 
Publication PUBMEDID
Libby EF, Frost AR, Demark-Wahnefried W, Hurst DR. Linking adiponectin and autophagy in the regulation of breast cancer metastasis. J Molec Med. 2014; epub Jun 7  24903246 
Cody JJ, Markert JM, Hurst DR. Histone deacetylase inhibitors improve the replication of oncolytic herpes simplex virus in breast cancer cells. PLoS One. 2014;9:e92919  24651853 
Khotskaya YB, Beck BH, Hurst DR, Han Z, Xia W, Hung MC, Welch DR. Expression of metastasis suppressor BRMS1 in breast cancer cells results in a marked delay in cellular adhesion to matrix. Mol Carcinog. 2013 Sep 2. doi: 10.1002/mc.22068.  24000122 
Diers AR, Vayalil PK, Oliva CR, Griguer CE, Darley-Usmar V, Hurst DR, Welch DR, Landar A. Mitochondrial bioenergetics of metastatic breast cancer cells in response to dynamic changes in oxygen tension: effects of HIF-1alpha;. PLoS One. 2013;8:e68348.  23840849 
Cody JJ, Hurst DR. Improving Oncolytic Herpes Simplex Virus for Metastatic Breast Cancer. J Genet Syndr Gene Ther 2013;4:1.   
Welch DR and Hurst DR. Unraveling the 'TGF-beta paradox' one metastamir at a time. Breast Cancer Res. 2013;15:305.  23448381 
Hurst DR, Xie Y, Thomas JW, Liu J, Edmonds MD, Stewart MD, Welch DR. The C-Terminal Putative Nuclear Localization Sequence of BReast cancer Metastasis Suppressor 1, BRMS1, Is Necessary for Metastasis Suppression. PLoS One. 2013;8:e55966.  23390556 
Hurst DR. Metastasis suppression by BRMS1 associated with SIN3 chromatin remodeling complexes. Cancer Metastasis Rev. 2012;31:641-51.  22678236 
Frost AR, Hurst DR, Shevde LA, Samant RS. The influence of the cancer microenvironment on the process of metastasis. Int J Breast Cancer. 2012;2012:756257.  22570792 
Cook LM, Cao X, Dowell AE, Debies MT, Edmonds MD, Beck BH, Kesterson RA, Desmond RA, Frost AR, Hurst DR, Welch DR. Ubiquitous Brms1 expression is critical for mammary carcinoma metastasis suppression via promotion of apoptosis. Clin Exp Metastasis. 2012;29:315-25.  22241150 
Ulasov IV, Kaverina NV, Pytel P, Thaci B, Liu F, Hurst DR, Welch DR, Sattar HA, Olopade OI, Baryshnikov AY, Kadagidze ZG, Lesniak MS. Clinical significance of KISS1 protein expression for brain invasion and metastasis. Cancer. 2012;118:2096-2105.  21928364 
Hurst DR and Welch DR. Unraveling the enigmatic complexities of BRMS1-mediated metastasis suppression. FEBS Lett. 2011;585:3185-90.  21827753 
Purushothaman A, Hurst DR, Pisano C, Mizumoto S, Sugahara K, Sanderson RD. Heparanase-mediated loss of nuclear syndecan-1 enhances histone acetyltransferase (HAT) activity to promote expression of genes that drive an aggressive tumor phenotype. J Biol Chem. 2011;286:30377-83.  21757697 
Lee S, Terry D, Hurst DR, Welch DR, Sang QX. Protein Signatures in Human MDA-MB-231 Breast Cancer Cells Indicating a More Invasive Phenotype Following Knockdown of Human Endometase/Matrilysin-2 by siRNA. J Cancer. 2011;2:165-76.  21475635 
Kwon YJ, Hurst DR, Steg AD, Yuan K, Vaidya KS, Welch DR, and Frost AR. Gli1 enhances migration and invasion via up-regulation of MMP-11 and promotes metastasis in ERalpha negative breast cancer cell lines. Clin Exp Metastasis. 2011;28:437-49.  21442356 
Hurst DR, Welch DR. Metastasis suppressor genes: at the interface between the environment and tumor cell growth. Int Rev Cell Mol Biol. 2011;286:107-80.  21199781 
Cook LM, Hurst DR, Welch DR. Metastasis suppressors and the tumor microenvironment. Semin Cancer Biol. 2011;21:113-22  21168504 
Hurst DR, Edmonds MD, Welch DR. Metastamir: the field of metastasis-regulatory microRNA is spreading. Cancer Res. 2009;69:7495-8.  19773429 
Edmonds MD, Hurst DR, Welch DR. Linking metastasis suppression with metastamiR regulation. Cell Cycle. 2009;8:2673-5.  19690456 
Edmonds MD, Hurst DR, Vaidya KS, Stafford LJ, Chen D, Welch DR. Breast cancer metastasis suppressor 1 coordinately regulates metastasis-associated microRNA expression. Int J Cancer. 2009;125:1778-85.  19585508 
Shin R, Welch DR, Mishra VK, Nash KT, Hurst DR, Rama Krishna N. Nuclear magnetic resonance and circular dichroism study of metastin (Kisspeptin-54) structure in solution. Clin Exp Metastasis. 2009;26:527-33.  19308666 
Richert MM, Vaidya KS, Mills CN, Wong D, Korz W, Hurst DR, Welch DR. Inhibition of CXCR4 by CTCE-9908 inhibits breast cancer metastasis to lung and bone. Oncol Rep. 2009;21:761-7.  19212637 
Hurst DR, Edmonds MD, Scott GK, Benz CC, Vaidya KS, Welch DR. Breast cancer metastasis suppressor 1 up-regulates miR-146, which suppresses breast cancer metastasis. Cancer Res. 2009;69:1279-83.  19190326 
Silveira AC, Hurst DR, Vaidya KS, Ayer DE, Welch DR. Over-expression of the BRMS1 family member SUDS3 does not suppress metastasis of human cancer cells. Cancer Lett. 2009;276:32-7.  19070953 
Welch DR, Cooper CR, Hurst DR, Lynch CC, Martin MD, Vaidya KS, VanSaun MN, Mastro AM. Metastasis Research Society-American Association For Cancer Research Joint Conference on Metastasis. Cancer Res. 2008;68:9578-82.  19047132 
Hurst DR, Xie Y, Edmonds MD, Welch DR. Multiple forms of BRMS1 are differentially expressed in the MCF10 isogenic breast cancer progression model. Clin Exp Metastasis. 2009;26:89-96.  18841483 
Vaidya KS, Harihar S, Phadke PA, Stafford LJ, Hurst DR, Hicks DG, Casey G, DeWald DB, Welch DR. Breast cancer metastasis suppressor-1 differentially modulates growth factor signaling. J Biol Chem. 2008;283:28354-60.  18664570 
Phadke PA, Vaidya KS, Nash KT, Hurst DR, Welch DR. BRMS1 suppresses breast cancer experimental metastasis to multiple organs by inhibiting several steps of the metastatic process. Am J Pathol. 2008;172:809-17.  18276787 
Hurst DR, Xie Y, Vaidya KS, Mehta A, Moore BP, Accavitti-Loper MA, Samant RS, Saxena R, Silveira AC, Welch DR. Alterations of BRMS1-ARID4A interaction modify gene expression but still suppress metastasis in human breast cancer cells. J Biol Chem. 2008;283:7438-44.  18211900 
Hurst DR, Welch DR. A MSC-ing link in metastasis? Nat Med. 2007;13:1289-91.  17987025 
Nash KT, Phadke PA, Navenot JM, Hurst DR, Accavitti-Loper MA, Sztul E, Vaidya KS, Frost AR, Kappes JC, Peiper SC, Welch DR. Requirement of KISS1 secretion for multiple organ metastasis suppression and maintenance of tumor dormancy. J Natl Cancer Inst. 2007;99:309-21.  17312308 
Hurst DR, Mehta A, Moore BP, Phadke PA, Meehan WJ, Accavitti MA, Shevde LA, Hopper JE, Xie Y, Welch DR, Samant RS. Breast cancer metastasis suppressor 1 (BRMS1) is stabilized by the Hsp90 chaperone. Biochem Biophys Res Commun. 2006;348:1429-35.  16919237 
Sang QX, Jin Y, Newcomer RG, Monroe SC, Fang X, Hurst DR, Lee S, Cao Q, Schwartz MA. Matrix metalloproteinase inhibitors as prospective agents for the prevention and treatment of cardiovascular and neoplastic diseases. Curr Top Med Chem. 2006;6:289-316.  16611144 
Hurst DR, Schwartz MA, Jin Y, Ghaffari MA, Kozarekar P, Cao J, Sang QX. Inhibition of enzyme activity of and cell-mediated substrate cleavage by membrane type 1 matrix metalloproteinase by newly developed mercaptosulphide inhibitors. Biochem J. 2005;392:527-36.  16026329 
Samant RS, Debies MT, Hurst DR, Moore BP, Shevde LA, Welch DR. Suppression of murine mammary carcinoma metastasis by the murine ortholog of breast cancer metastasis suppressor 1 (Brms1). Cancer Lett. 2006;235:260-5.  15978719 
Hurst DR, Schwartz MA, Ghaffari MA, Jin Y, Tschesche H, Fields GB, Sang QX. Catalytic- and ecto-domains of membrane type 1-matrix metalloproteinase have similar inhibition profiles but distinct endopeptidase activities. Biochem J. 2004;377:775-9.  14533979 
Park HI, Jin Y, Hurst DR, Monroe CA, Lee S, Schwartz MA, Sang QX. The intermediate S1' pocket of the endometase/matrilysin-2 active site revealed by enzyme inhibition kinetic studies, protein sequence analyses, and homology modeling. J Biol Chem. 2003;278:51646-53.  14532275 
Wei P, Zhao YG, Zhuang L, Hurst DR, Ruben S, Sang QX. Protein engineering and properties of human metalloproteinase and thrombospondin 1. Biochem Biophys Res Commun. 2002;293:478-88.   12054626 
Hurst DR, Li H, Xu X, Badisa VL, Shi YE, Sang QX. Development and
characterization of a new polyclonal antibody specifically against tissue inhibitor of metalloproteinases 4 in human breast cancer. Biochem Biophys Res Commun. 2001;281:166-71. 
11178975 

Keywords
metastasis, breast cancer, chromatin remodeling, microenvironment, tumor progression