Markus Frank's laboratory defined a novel function for ABCB5 in cancer stem cell maintenance and tumor growth, and investigates the therapeutic efficacy of ABCB5 targeting in melanoma and additional ABCB5-expressing human malignancies.

Research in the Markus Frank lab focuses on the physiological and pathological roles of the P-glycoprotein family of ATP-binding cassette (ABC) multidrug resistance transporters. His laboratory cloned and characterized the third member of this human gene family, ABCB5, which marks progenitor subpopulations in human skin and cancer stem cells in human malignant melanoma.

The group showed that ABCB5 functions as a drug-resistance mediator in human melanoma. They also demonstrated that specific targeting of ABCB5 can sensitize melanoma cells to chemotherapy. In subsequent work, they discovered that ABCB5 expression identifies malignant melanoma-initiating cells (MMICs) that correlate with tumorigenic growth in vivo, and that ABCB5 is more abundant in human malignant melanoma than in benign melanocytic nevi in human patients.

The Frank laboratory demonstrated that ABCB5-positive MMICs can be specifically targeted to inhibit tumor growth, providing proof-of-principle for the potential therapeutic utility of the cancer stem cell concept.

Further, they provided evidence for immunomodulatory functions of human cancer stem cells. Although MMICs with a key role in tumor formation and growth can be immunologically targeted to inhibit tumor development, they also express biomolecules that are immunoprotective. Thus, MMICs serve specific roles in evasion of antitumor immunity and melanoma immunotherapeutic resistance.

In tandem with fundamental approaches to further dissect the functional roles of ABCB5 in physiological and cancer stem cells, Dr. Frank's laboratory explores the clinical relevance of ABCB5 as a biomarker of melanoma progression, prognosis, and outcome, and investigates the therapeutic efficacy of ABCB5 targeting in human malignant melanoma.

Biosketch

Markus Frank is Associate Professor of Pediatrics and of Dermatology at Harvard Medical School, Associate Physician of Medicine at Brigham and Women's Hospital, a member of the Stem Cell Program at Boston Children's Hospital, and co-leader of the HSCI Skin Program.

Frank received a Bachelor’s degree in Biochemical Sciences from Harvard College and an M.D. degree from the University of Heidelberg School of Medicine, Germany. He completed a residency in Internal Medicine at Albert Einstein College of Medicine in New York and a fellowship in Nephrology at Brigham and Women's Hospital, followed by research training in transplant immunology at Brigham and Women's Hospital and Boston Children's Hospital. He is an elected member of the American Society for Clinical Investigation (ASCI).

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