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Faculty Detail    
Name DOUGLAS R HURST
  
Campus Address VH G019 Zip 0019
Phone  (20-5) -951
E-mail  douglashurst@uabmc.edu
Other websites Publications via PubMed
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Faculty Appointment(s)
Appointment Type Department Division Rank
Primary  Pathology   Molecular & Cellular Pathology Associate Professor
Center  Comprehensive Cancer Center  Comprehensive Cancer Center Associate Professor
Center  General Clinical Research Center  Ctr for Clinical & Translational Sci Associate Professor

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

Biographical Sketch 
Prior to receiving his degrees, Dr. Hurst served in the US Navy for 6 years as a SCUBA diver and nuclear mechanic onboard the fast attack nuclear submarine USS Grayling (SSN-646). After an honorable discharge from the Navy, Dr. Hurst earned a BS in Biochemistry and BA in Chemistry from the College of Charleston in Charleston, South Carolina where he published several papers from his undergraduate research related to the strong-base synthesis of heterocyclic aromatic compounds. He then received an individual pre-doctoral fellowship from the Department of Defense Breast Cancer Research Program (scored 1.0) entitled "Targeting Breast Cancer Membrane Metalloproteinases" under the mentorship of Dr. QX Amy Sang at Florida State University in Tallahassee, Florida. After completion of his PhD in Biochemistry, he moved to the University of Alabama at Birmingham where he obtained an individual Ruth L. Kirschstein post-doctoral fellowship from NIH (F32) entitled "Mechanistic Insight into BRMS1 Suppression of Metastasis" under the mentorship of Dr. Danny Welch. In December of 2010, he became an Assistant Professor in the Department of Pathology where his current studies are focused on understanding the molecular mechanisms of breast cancer metastasis.

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/ 
Metastasis Research Society  past board member  http://www.metastasis-research.org/ 
Susan G. Komen North Central Alabama  board member - president elect  http://www.komenncalabama.org/ 
 



Research/Clinical Interest
Title
Molecular mechanisms of cancer metastasis
Description
The overall goal of our studies is to understand the molecular mechanisms of cancer metastasis. Many metastasis-associated genes are epigenetically regulated by chromatin structure. A major ongoing project in our group is to functionally characterize how SIN3 chromatin modification complexes regulate breast cancer progression and metastasis. SIN3 is a nuclear scaffold that recruits transcription factors, histone binding proteins, and protein modifying enzymes to specific sites of chromatin leading to epigenetic regulation of gene transcription. There are two paralogs of SIN3 in higher organisms that are located on different chromosomes. We discovered that SIN3 paralogs, SIN3A and SIN3B, play divergent roles in regulating triple negative breast cancer progression and our data suggest that SIN3B expression is required for metastasis and SIN3A is a metastasis suppressor. Our projects include basic molecular and cellular biology techniques using both in vitro and in vivo model systems to characterize the structural and functional units of SIN3 complexes. To determine the clinical relevance of our data, we utilize patient tissue samples in translational studies. We have been funded extramurally by the American Cancer Society, METAvivor Research and Support, and the Elsa U. Pardee Foundation.

Selected Publications 
Publication PUBMEDID
Welch DR and Hurst DR. Beyond the Primary Tumor: Progression, Invasion and Metastasis. In: The Molecular Basis of Human Cancer, 2nd Edition. Eds. W.B. Coleman and G.J. Tsongalis. The Humana Press. 2017; pp 203-216.   
Cody JJ, Hurst DR. Improving Oncolytic Herpes Simplex Virus for Metastatic Breast Cancer. J Genet Syndr Gene Ther. 2013;4:1.   
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 
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 
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 
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 
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, 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 
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, 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 
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, Welch DR. A MSC-ing link in metastasis? Nat Med. 2007;13:1289-91.  17987025 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
Edmonds MD, Hurst DR, Welch DR. Linking metastasis suppression with metastamiR regulation. Cell Cycle. 2009;8:2673-5.  19690456 
Hurst DR, Edmonds MD, Welch DR. Metastamir: the field of metastasis-regulatory microRNA is spreading. Cancer Res. 2009;69:7495-8.  19773429 
Cook LM, Hurst DR, Welch DR. Metastasis suppressors and the tumor microenvironment. Semin Cancer Biol. 2011;21:113-22  21168504 
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 
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 
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 
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 
Hurst DR and Welch DR. Unraveling the enigmatic complexities of BRMS1-mediated metastasis suppression. FEBS Lett. 2011;585:3185-90.  21827753 
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 
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 
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 
Hurst DR. Metastasis suppression by BRMS1 associated with SIN3 chromatin remodeling complexes. Cancer Metastasis Rev. 2012;31:641-51.  22678236 
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 
Welch DR and Hurst DR. Unraveling the 'TGF-beta paradox' one metastamir at a time. Breast Cancer Res. 2013;15:305.  23448381 
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 
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. 2014;53:1011-26.  24000122 
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 
Libby EF, Frost AR, Demark-Wahnefried W, Hurst DR. Linking adiponectin and autophagy in the regulation of breast cancer metastasis. J Molec Med. 2014;92:1015-23.  24903246 
Yu H, Liu Y, McFarland BC, Deshane JS, Hurst DR, Ponnazhagan S, Benveniste EN, Qin H. SOCS3 Deficiency in Myeloid Cells Promotes Tumor Development: Involvement of STAT3 Activation and Myeloid-Derived Suppressor Cells. Cancer Immunol Res. 2015;3:727-40  25649351 
Falk Libby E, Liu J, Li YI, Lewis MJ, Demark-Wahnefried W, Hurst DR. Globular adiponectin enhances invasion in human breast cancer cells. Oncol Lett. 2016;11:633-641.  26870258 
Li YI, Libby EF, Lewis MJ, Liu J, Shacka JJ, Hurst DR. Increased autophagic response in a population of metastatic breast cancer cells. Oncol Lett. 2016;12:523-529.  27347175 
Cody JJ, Hurst DR. Promising oncolytic agents for metastatic breast cancer treatment. Oncolytic virotherapy. 2015;4:63-73.  27512671 
Welch DR, Manton CA, Hurst DR. Breast Cancer Metastasis Suppressor 1 (BRMS1): Robust Biological and Pathological Data, But Still Enigmatic Mechanism of Action. Adv Cancer Res. 2016;132:111-37.  27613131 
Lewis MJ, Liu J, Libby EF, Lee M, Crawford NP, Hurst DR. SIN3A and SIN3B differentially regulate breast cancer metastasis. Oncotarget. 2016;7:78713-78725.  27780928 
Fingleton B, Lange K, Caldwell B, Bankaitis KV; Board of the Metastasis Research Society. Perspective on the interpretation of research and translation to clinical care with therapy-associated metastatic breast cancer progression as an example. Clin Exp Metastasis. 2017;34:443-447.   29484519 
Welch DR and Hurst DR. Defining the hallmarks of metastasis. Cancer Res. 2019;79:3011-3027.  31053634 
 

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