Student Directory

Hometown: Arlington, VA

Undergraduate Education:  BA/02 Biomedical Engineering/Vanderbilt

Research Interest:  Molecular signaling cascade involved in UVB- and chemically-induced skin carcinogenesis

Advisor: Lisa Shantz, PhD
Graduate Program: Physiology

Thesis:

Description: Nonmelanoma skin cancer (NMSC) is the most prevalent cancer worldwide, accounting for more than 40% of all cancers diagnosed every year. Human skin is constantly exposed to ultraviolet (UV) irradiation, which causes DNA damage, skin aging, and skin cancer. Apoptosis is essential to eliminate damaged skin cells harboring oncogenic mutations; however, keratinocytes and their stem cells have evolved mechanisms protecting cells against apoptosis. These mechanisms preserve cellular homeostasis and epidermal integrity but can also serve as a pathway for skin cells to progress to NMSC.

The Akt/mTOR pathway is known to regulate cell growth and differentiation, and activate pro-survival/anti-apoptotic signaling cascades. Studies have shown mTOR activation occurs at much higher levels in human epidermal tumors relative to actinic keratosis or normal skin, suggesting that mTOR signaling might be a useful therapeutic target. In addition, renal transplant recipients receiving rapamycin, an inhibitor of mTOR, had significantly lower incidences of squamous cell carcinoma (SCC) compared with patients on alternative immuno suppressive agents. Collectively, these results suggest that a better understanding of mTOR's role in epidermal cells with relation to tumor initiating and promoting agents is needed, and may lead to the identification of targets for chemoprevention of NMSC. We hypothesize that selectively inhibiting components of the mTOR pathway will inhibit skin tumorigenesis by both increasing the sensitivity of keratinocytes and their progenitors to apoptotic signaling and blocking proliferation and clonal expansion of initiated cells.

Meeting Presentations

• 2001
  NIH Summer Research Poster Session, NIH, Bethesda, MD
• 2004
  AACR Annual Meeting, Orlando, FL
• 2009
  Penn State College of Medicine Graduate Research Forum, Hershey, PA
  Genetics Symposium, Penn State University, Hershey, PA
  Gordon Research Conference on Polyamines, Waterville Valley, NH
• 2010
  Penn State College of Medicine Graduate Research Forum, Hershey, PA
  International Skin Carcinogenesis Conference, State College, PA
• 2011
  Penn State College of Medicine Graduate Research Forum, Hershey, PA
  Gordon Research conference on Polyamines, Waterville Valley, NH
  National MD/PhD Student Conference, Keystone, CO
• 2012
  AACR:  American Association of Cancer Research Annual Meeting, Chicago, IL
  Penn State College of Medicine Graduate Research Forum, Hershey, PA (poster)

Molloy FM, Carr TD, Zeuner KE, Dambrosia JM, Hallett M (2003) Abnormalities of spatial discrimination in focal and generalized dystonia Brain 126(10):2175-2182 PMID: 12821512

Spruessel A, Steinmann G, Jung M, Lee SA, Carr T, Fentz AK, Spangenberg J, Zornig C, Juhl HH, David KA (2004) Tissue ischemia time affects gene and protein expression patterns within minutes following surgical tumor excision Biotechniques 36(6):1030-7 PMID: 15211754

Espinoza L, Valikhani M, Carr T, Jung M, Hyde J, Witten M, Smulson M (2004) Altered expression of gamma-synuclein and detosification-related genes in lungs of rats exposed to JP-8 Am J of Resp Cell & Mol Biol 32(3):192-200 PMID: 15618438

Mewani RR, Tian S, Li B, Danner MT, Carr TD, Lee S, Rahman A, Kasid UN, Jung M, Dritschilo A, Gokhale PC (2006) Gene expression profile by inhibiting Raf-1 protein kinase in breast cancer cells  Int J Mol Med 17(3):457-63 PMID: 16465392

Zhang Y, Carr T, Dimtchev A, Zaer N, Dritschilo A, Jung M (2007) Attenuated DNA damage repair by trichostatin A through BRCA1 suppression  Radiat Res 168(1): 115-24 PMID: 17722998