Member, Tumor Signaling and Angiogenesis
Professor of Physiology, Oral Biology, Graduate Studies, Cellular Biology and Anatomy, Medicine (Dermatology) and Orthopedic Surgery
Georgia Cancer Center
1467 Laney Walker Blvd., CA-1008
My laboratory is interested in the signals that regulate normal cell processes and what goes wrong in cancer, with the idea that prevention of cancer may be as effective, or perhaps even more effective, than treatment of the disease. In particular, I study the signaling mechanisms that regulate the growth (proliferation) and maturation (differentiation) of epidermal keratinocytes, the primary cell constituents of the outer layer of the skin, the epidermis. Keratinocytes can transform into the non-melanoma skin cancers, which are the most common cancers in the world, with approximately three million new cases diagnosed each year in the United States alone. While most non-melanoma skin cancers are remedied by surgical removal, treatment is often disfiguring as these cancers occur mostly on visible skin. My laboratory has identified one signal that promotes keratinocyte growth, maturation and survival while another signaling pathway that we study inhibits growth and promotes maturation, and both are abnormal in non-melanoma skin cancers.
Protein Kinase D in Epidermal Keratinocyte Proliferation, Differentiation, Survival
My laboratory investigates the signaling mechanisms that regulate the proliferation and differentiation of epidermal keratinocytes and the role of these mechanisms in the development of non-melanoma skin cancers. The etiology of the non-melanoma skin cancers is not entirely understood, although the most important risk factor for these cancers is chronic sun exposure, that is, ultraviolet (UV) radiation. We are studying the involvement of protein kinase D in promoting keratinocyte proliferation and survival and inhibiting differentiation. We previously showed that protein kinase D levels are increased in the non-melanoma skin cancer basal cell carcinoma, that protein kinase D is activated by UV irradiation of epidermal keratinocytes and that this activated protein kinase D protects keratinocytes from UV-induced cell death (apoptosis). Thus, our results provide a potential link between protein kinase D, sun-induced non-melanoma skin cancers and epidermal tumorigenesis. We are currently examining the mechanism by which protein kinase D protects keratinocytes from UV-induced apoptosis.
The Phospholipase D2-Aquaporin-3 Signaling Module in Epidermal Keratinocyte Proliferation, Differentiation and Tumorigenesis
On the other side of the equation, my laboratory has also found evidence of the involvement of another pathway in inhibiting keratinocyte proliferation and stimulating differentiation. This pathway is composed of the lipid-metabolizing ezyme phospholipase D2 (PLD2) and the glycerol transporter aquaporin-3 (AQP3). PLD2 is able to convert the glycerol transported by AQP3 into the lipid signal phosphatidylglycerol (PG), which can regulate keratinocyte growth and maturation. Furthermore, the levels of AQP3 and/or PLD2 are abnormal in the non-melanoma skin cancers, suggesting a potential role in cancer development in the skin. AQP3 may also be involved in the skin disease psoriasis, which is characterized by excessive (non-cancerous) proliferation of keratinocytes, abnormal keratinocyte differentiation and skin inflammation. In both cases we are investigating the regulation of the pathway components as well as the mechanisms by which these factors act to regulate keratinocyte and skin function
Other Areas of Interest
Finally, my laboratory collaborates with a number of other laboratories to understand the cell signaling mechanisms that regulate various other cell processes, including breast, prostate and metastatic colon cancer cell proliferation and/or cell death (apoptosis), as well as hormone secretion, bone formation and corneal epithelial wound healing.
VA Merit Bollag (PI) 07/01/16-06/30/20
Veterans Administration 6 calendar months
“Epidermal Aquaporin-3 in Psoriasis”
The aim of this award is to determine the role of aquaporin-3 in psoriasis and the effect of aquaporin-3-transported glycerol in this disease.
P01 AG27175 Isales (PI)
NIH/NIA 1.2 calendar months
“Age-induced Impairment of Nutrient Signaling Results in Bone Loss”
The aim of this program project is to determine the role of nutrients in regulating bone formation by mesenchymal stem cells and osteoblasts and the decrease observed with aging.
Role: Co-Investigator on Project #1