Department of Microbiology and Immunology
Microbiology and Immunology
1995-2000 Postdoctoral Fellow, MUSC
1995 Ph.D., North Carolina State University
Tissue homeostasis is a balance between life (cell growth) and death (apoptosis). When this balance is lost, uncontrolled cell growth leads to cancer and threatens the organism. The long-term goal of my lab is to understand signal transduction pathways leading to cell death and to modulate these pathways in an effort to improve cancer therapies. Specific areas of research include (1) sphingolipids, (2) oxidative stress and (3) gene delivery systems.=
(1) Sphingolipids in apoptosis - Ceramide is a metabolite of sphingolipid metabolism that is involved in numerous physiological responses, including apoptosis. We have shown that modulation of ceramide synthase 6 (CerS6/LASS6), which preferentially generates C16-ceramides, can influence susceptibility to cell death. Mechanisms by which changes in CerS6 expression affect cellular signaling during cell death are under investigation.
(2) Oxidative stress, which is prevalent in the tumor microenvironment, can influence the apoptotic potential of tumor cells as well as therapeutic T cells. We are investigating how modulation of anti-oxidant capacity alters cell death responses and how this impacts on cancer therapy.
(3) Delivery of therapeutic genes remains one of the challenges of cancer therapy. In collaboration with Dr. Kaushal Rege (Arizona State University), we are investigating gene delivery using polymer-conjugated adenovirus hybrids and nanoparticle mediated delivery.
Recent Publications | Additional Publications
Kasman LM, Barua S, Lu P, Rege K, Voelkel-Johnson C. Polymer-enhanced adenoviral transduction of CAR-negative bladder cancer cells. Mol Pharm. 2009 Sep-Oct;6(5):1612-9. PubMed PMID: 19655763; PubMed Central PMCID: PMC2757475.
Walker T, Mitchell C, Park MA, Yacoub A, Rahmani M, Häussinger D, Reinehr R, Voelkel-Johnson C, Fisher PB, Grant S, Dent P. 17-allylamino-17-demethoxygeldanamycin and MEK1/2 inhibitors kill GI tumor cells via Ca2+-dependent suppression of GRP78/BiP and induction of ceramide and reactive oxygen species. Mol Cancer Ther. 2010 May;9(5):1378-95. Epub 2010 May 4. PubMed PMID: 20442308; PubMed Central PMCID: PMC2868106.
Norell H, Martins da Palma T, Lesher A, Kaur N, Mehrotra M, Naga OS, Spivey N, Olafimihan S, Chakraborty NG, Voelkel-Johnson C, Nishimura MI, Mukherji B, Mehrotra S. Inhibition of superoxide generation upon T-cell receptor engagement rescues Mart-1(27-35)-reactive T cells from activation-induced cell death. Cancer Res. 2009 Aug 1;69(15):6282-9. Epub 2009 Jul 28. PubMed PMID: 19638595; PubMed Central PMCID: PMC2719828.
White-Gilbertson SJ, Kasman L, McKillop J, Tirodkar T, Lu P, Voelkel-Johnson C. Oxidative stress sensitizes bladder cancer cells to TRAIL mediated apoptosis by down-regulating anti-apoptotic proteins. J Urol. 2009 Sep;182(3):1178-85. Epub 2009 Jul 21. PubMed PMID: 19625063; PubMed Central PMCID: PMC2749573.
Title: TRAIL-Induced Apoptosis in Prostate Cancer
Funding Period: 4/1/2004 - 2/28/2011
Title: Mechanisms of Sensory Hair cell Death and Survival
Funding Period: 7/1/2010 - 6/30/2015
Title: Targeted Polymer-Adenovirus Hybrids for Ablation of Bladder Cancer Disease
Funding Period: 8/1/2010 - 7/31/2012
Title: Engineering DNA Delivery Polymers using Combinatorial and Cheminformatics Methods
Funding Period: (anticipated funding period 12/1/2010 - 11/30/2015)