Natasha Y. Frank, MD
Dr. Frank’s laboratory research explores the biology of stem cells and their roles in physiologic organogenesis, repair and malignant transformation, with the ultimate goal of developing novel stem cell-targeted strategies in the fields of tissue regeneration and cancer. Dr. Frank originally cloned and characterized the novel ATP-binding cassette transporter, ABCB5, and showed that this plasma membrane-expressed P-glycoprotein homologue functions in self-renewal and maintenance of slow-cycling adult stem cells and multidrug-resistant cancer stem cells, through stabilization of p53 and regulation of anti-apoptotic signaling pathways. For example, in the mammalian eye, ABCB5 is essential for corneal development and repair through regulation of limbal stem cell (LSC) maintenance and survival (Ksander et al. Nature 2014). Importantly, Dr. Frank’s laboratory also showed that purified ABCB5-positive LSC grafts are capable of fully restoring the cornea in preclinical models of limbal stem cell deficiency (LSCD), providing a clear rationale for clinical transplantation trials involving this stem cell population to improve therapy for LSCD and potentially additional corneal disorders. In human cancer, ABCB5 has also been shown to control stem cell maintenance and to be responsible for cancer stem cell-driven tumor initiation, drug resistance and metastatic disease progression. Specifically, Dr. Frank’s laboratory established that ABCB5 confers clinical drug resistance to the first-line chemotherapeutic agent, 5-fluoruracil, on colorectal cancer stem cells (Wilson et al. Cancer Res. 2011); as a result, her laboratory now seeks to further dissect ABCB5 functions in colorectal cancer stem cells and to target newly discovered ABCB5 anti-apoptotic functions in this malignancy to ultimately improve clinical colorectal cancer therapy.