Laura Timares, Ph.D.


Photo Timares headshot2005 sml

University of Alabama at Birmingham
BMR2 404 (courier)
BMR2 502 (post)
901 19th Street South
BIRMINGHAM AL 35294-2127

Office: (205)934-7545
FAX: (205)975-7949
timares@uab.edu

 






Education

B.S.                 University of California at Los Angeles, 1982
Ph. D.              UCLA School of Medicine, 1990
Fellowship     Post-doctoral Fellow, California Institute of Technology, 1991 -
                         1993

 Academic Appointments

Associate Professor:   Department of Dermatology
Assistant Professor:   Department of Cell Biology
Assistant Professor:   Department of Pathology
Associate Scientist:    Gene Therapy Center 
Associate Scientist:    Comprehensive Cancer Center 
Director:     UAB Skin Diseases Research Center, Skin Cell Culture Core 


Research Focus

With the goal of developing effective topical vaccines, we are currently studying cutaneous (a.k.a., skin-derived) DCs, termed Langerhans cells (LCs). This subset of DCs may have a specialized function in delivering cutaneous antigens to draining lymph nodes where they orchestrate either tolerogenic or immunogenic responses. Recently, we discovered that murine LCs undergo cell death after successful antigen presentation to naive T cells and this limits their immunogenic potential to combat infectious diseases or cancer. We have identified the pertinent apoptosis-signaling cascade used by LCs in response to T cells as "Type II", requiring the pro-apoptotic molecule Bid. In the absence of Bid, LCs are resistant to T cell-induced death as well as mechanisms of UV radiation-induced tolerance and perform as superior vaccinating agents. How such gene-modified, apoptosis-resistant DCs induce enhanced T cell responses, evade induction of regulatory T cells (Treg) development, and the molecular signals used by T cells to trigger DC death are under current investigation.

We have also shown that epidermal keratinocytes depend on Bid expression as a tumor suppressor to protect against the development of UV-induced cutaneous neoplasias. We have evidence that Bid has a novel pro-survival function that may promote cell cycle checkpoints to promote DNA repair after UV damage. We are investigating the novel molecular mechanism by which Bid promotes cell survival in normal and skin tumor cells with the hope of identifying a new pathway that may be important to target with anti-cancer drugs.

In addition, we are developing and testing novel adenoviral vectors that target delivery of genes to dendritic cells and epidermal skin cells to modulate the immune system or ameliorate disease. We are working closely with colleagues in the Gene Therapy Center to test the efficacy of these adenoviral vectors in unique and clinically relevant animal models.

 

Selected Peer Reviewed Publications

 Pradhan, S, J. Genebriera, K. Felix, W. Denning, C.A. Elmets and L. Timares. (2006). CD4 T cell-induced, Bid-dependent apoptosis in cutaneous dendritic cells regulates T cell expansion and immune responses. Journal of Immunology 177(9): 5956-5967.

Pradhan S. , H.K. Kim, C.J. Thrash, M.A. Cox, S. Mantena, J.-H. Wu, M. Athar, S.K.  Katiyar, C.A. Elmets, L. Timares.   (2008). A critical role for the proapoptotic protein Bid in UV-induced immune suppression and cutaneous apoptosis. J Immunol. 1;181(5):3077-88.

 Xu J, Timares L, Heilpern C, Weng Z, Li C, Xu H, Pressey J, Elmets C, Kopelovich L, Athar M. (2010) Targeting wild-type and mutant p53 with small molecule CP-31398 blocks the growth of rhabdomyosarcoma by inducing ROS-dependent apoptosis. Cancer Research 15;70(16):6566-76.

Hui, Xu, Laura Timares, Craig A. Elmets.  (2011) Chapter 18. Host defenses in skin. In: Clinical Immunology, 4th Edition.  Rich, Frew and Weyland , Editors.

Nasti TH, Timares L. (2012) Inflammasome activation of IL-1 family mediators in response to cutaneous photodamage. Photochemistry and Photobiology 2012 Sep-Oct;88(5):1111-25. [Figure chosen for Journal Cover]

 Lebow, L. T.  and  B. Bonavida.  (1990).   Purification and characterization of cytolytic and noncytolytic human natural killer cells.  Proceedings of the National Academy of Science USA   87:6063-6067

Timares, L., A. Takashima, and S.A. Johnston. (1998).  Quantitative analysis of the immunopotency of genetically transfected dendritic cells.  Proceedings of the National Academy of Science USA.  22: 13147-13152.

Timares L., K.M. Safer, B. Q., A. Takashima,  S.A. Johnston. (2003). Drug-inducible, dendritic cell-based genetic immunization. Journal of Immunology 170:5483-5490.

Timares L, Douglas JT, Tillman BW, Krasnykh V, Curiel DT (2004). Adenovirus-mediated gene delivery to dendritic cells. Methods Mol Biol. 246:139-54.

*Timares, L., S. K. Katiyar, C. A. Elmets.  (2008). DNA Damage, Apoptosis and Langerhans Cells—Activators of UV-induced Immune Tolerance. Photochemistry and Photobiology 84(2):422-436. (*invited – peer reviewed) [Figure chosen for Journal Cover ].

Yusuf, N., T. H. Nasti, S. K. Katiyar, M. K. Jacobs, M. D. Seibert, A. C. Ginsburg, L. Timares, H Xu, C. A. Elmets. (2008). Antagonistic roles of CD4+ and CD8+ T cells in DMBA cutaneous carcinogenesis. Cancer Res. 15;68(10):3924-30.    

Thacker EE, Nakayama M, Smith BF, Bird RC, Muminova Z, Strong TV, Timares L, Korokhov N, O'Neill AM, de Gruijl TD, Glasgow JN, Tani K, Curiel DT. (2009). A genetically engineered adenovirus vector targeted to CD40 mediates transduction of canine dendritic cells and promotes antigen-specific immune responses in vivo. Vaccine 27(50):7116-24

Matthews Q, Fatima A, Tang Y, Perry B, Tsuruta Y, Komarova S, Timares L, Zhao C, Makarova N, Borovjagin A, Stewart P, Wu H, Blackwell J, Curiel DT.  (2010) HIV Antigen Incorporation within Adenovirus Hexon Hypervariable 2 for a Novel HIV Vaccine Approach. PloSONE 5(7):e11815.

Xu J, Timares L, Heilpern C, Weng Z, Li C, Xu H, Pressey J, Elmets C, Kopelovich L, Athar M. (2010) Targeting wild-type and mutant p53 with small molecule CP-31398 blocks the growth of rhabdomyosarcoma by inducing ROS-dependent apoptosis. Cancer Research 15;70(16):6566-76.

Walsh SB, Xu J, Xu H, Kurundkar AR, Maheshwari A, Grizzle WE, Timares L, Huang CC, Kopelovich L, Elmets CA, Athar M. (2011) Cyclosporine a mediates pathogenesis of aggressive cutaneous squamous cell carcinoma by augmenting epithelial-mesenchymal transition: Role of TGFβ signaling pathway. Mol Carcinog. 50(7):516-27.

Click here for pubmed link to further publications


Active Grant Support

National Institutes of Health/National Institute of Arthritis and Musculoskeletal and  Skin Diseases
Project entitled "UAB Skin Diseases Research Center Core B: Skin Cell Culture Core".

Period: 09/01/09 - 08/31/14
Core Director

National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases
Project entitled"TCR V repertoire sequence analysis to identify diagnostic psoriasis-specific CDR3 sequences."
Period: 09/01/2013-08/31/2014
PI

Department of Veterans Affairs Merit Award, Craig Elmets, M.D. (PI)
Project entitled "Host defense mechanisms in polyaromatic hydrocarbon carcinogenesis."
Period: 10/01/10 - 09/30/14
Co-Investigator

                                                                                                                 

National Institutes of Health/National Cancer Institute, Mohammad Athar, Ph.D. (PI)
Project entitled " Inhibiting mulitple molecular targets for preventing non-melanoma skin cancer."

Period: 03/01/2011-02/28/2016                                                                                                                                                                
Co-Investigator

 National Institutes of Health/NIAID, Matthews (PI)
Project entitled: " Chimeric Adenoviruses for an improved HIV vaccine."
Period: 01/01/2011-12/31/2015
Co-Investigator