Ph.D., Cell & Molecular Biology
Texas Tech University
| Hepatocellular carcinoma|| inflammation|
| hepatocyte proliferation|| protein turnover|
| AMPK|| p27Kip1|
The research in Dr. Short's laboratory is focused on primary liver cancer, which is mostly comprised of hepatocellular carcinoma (HCC). HCC is the sixth most common cancer worldwide and ranks third in cancer-related mortalities, having a 5-year survival rate of less than 10%. In the United States, the incidence rate and mortality rate of liver cancer has increased over the past three decades and are higher in ethnic/racial minority groups (male and female) when compared to non-minorities – in Hispanic populations, both the incidence and death rate from hepatocellular carcinoma are significantly higher than those seen in non-Hispanics. Therefore, development of effective therapies that prevent, slow or abolish liver cancer development is a high-priority goal toward abolition of cancer mortality in general and in improving the health of Hispanic populations in particular. Most of the predisposing conditions for HCC, including Hepatitis B or Hepatitis C infection or alcohol-induced liver disease, involve chronic liver disease and cirrhosis, whereby inflammatory mediators induce hepatocytes to enter a hyperproliferative state. Therefore, Dr. Short's research is focused on the identification of compounds that prevent the production of inflammatory cytokines in the liver or compounds that prevent the inflammatory cytokine-induced proliferation of hepatocytes.
Dr. Short's previous work focused on the role of the AMP-activated Protein Kinase (AMPK) enzyme, a heterotrimeric Serine/Threonine kinase that is activated in response to decreased intracellular energy levels, in non-hepatic tumors. His previous work, and work from others, showed that AMPK activation alters the stability and subcellular localization of the p27Kip1 protein, which is a cyclin-dependent kinase inhibitor (CKI) that participates in regulation of the G1- to S-phase transition of the cell cycle. Furthermore, the lab found that AMPK-mediated phosphorylation of p27Kip1 not only controls cell division, but also plays a role in preventing cellular apoptosis and/or promoting cellular autophagy in certain cellular contexts. These results identified the AMPK enzyme and the p27Kip1 protein as primary participants in certain intracellular events that give rise to, or maintain, the development of tumors from normal cells (intracellular stress, increased proliferation, and/or failure of abnormal cells to undergo apoptosis). In contrast, the antidiabetic drug Metformin, which activates the AMPK enzyme, has been shown to prohibit HCC development, and AMPK-activating compounds, including Metformin and aminoimidazole carboxamide ribonucleotide (AICAR), have been shown to alter the growth of liver tumor cell lines. In addition, loss of p27Kip1 (which occurs frequently in patients with HCC) was shown to promote liver tumorigenesis in vivo in C57BL/6 mice, a strain of mice that is normally resistant to liver tumorigenesis. Therefore, Dr. Short is interested in elucidating the role that both the AMPK signaling pathway and p27Kip1 (or other AMPK target proteins) play in the progression of HCC and in response to treatment of HCC with AMPK-activating compounds.
Appointments, Boards, Committees and Memberships
American Association for the Study of Liver Diseases (AASLD) - 01/2012-01/2013
American Society for Biochemistry and Molecular Biology - 09/2012-Present
UTHSCSA Faculty Senate Representative for Basic Sciences - 2012-Present
E-RAHC Journal Club Meeting Organizer - 2011-2013
Library Liaison, University of Texas Health Science Center at San Antonio, Regional Academic Health Center - 2010-2013
Books and Publications
Manuscript Reviews - American Journal of Physiology-Renal Physiology
Manuscript Reviews - Molecules
Lectures and Presentations
American Chemical Society Spring 2012 National Meeting and Symposium - 'Bismuth nitrate-induced novel nitration of estradiol: an entry to new anticancer agents - San Diego, CA.
American Chemical Society Spring 2012 National Meeting and Symposium - 'Synthesis of Pyrenyl compounds as potential anticancer agents' - San Diego, CA.
Texas A&M Health Science Center (Host: Dr. Cheryl Lyn Walker) - 2012 - Houston, TX.
241st American Chemical Society National Meeting and Exposition 2011 - 'Ultrasound-assisted, bismuth nitrate-catalyzed expeditious synthesis and biological evaluation of N-substituted pyrrole derivatives' - Anaheim, CA.
241st American Chemical Society National Meeting and Exposition 2011 - 'Synthesis and biological evaluation of new polyaromatic anticancer agents' - Anaheim, CA.