Theresa A. Guise, MD was recruited to The University of Texas M.D. Anderson Cancer Center from an Indiana University School of Medicine through a Recruitment of Established Investigators Award. She has a strong history of successful extramural funding, with continuous NIH support since 1993.

Throughout her career, Dr. Guise has made seminal contributions to our understanding of cancer effects on the musculoskeletal system, beginning with demonstrating the central role for tumor–secreted PTHrP, and its downstream mediator, RANKL, in osteolytic bone metastases. These studies were the first to provide the rationale for RANKL antibodies to treat bone metastases, now FDA approved for all solid tumor metastases to bone and multiple myeloma. She developed the first animal models of osteoblastic metastases that defined the causal role of endothelin-1, and described the role of bone-derived TGF Beta in promoting bone metastases of multiple solid tumors. She showed that bone microenvironment hypoxia enhanced TGF Beta signaling to promote bone metastases and identified an inhibitor of TGF Beta signaling, PMEPA1, which is regulated in prostate cancer and whose expression predicts metastases-free survival. Recently, she has shown that bone-derived TGF Beta induces oxidation of the skeletal muscle intracellular calcium release channel (ryanodine receptor) causing calcium leak & muscle weakness.

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Theresa A. Guise, MD was recruited to The University of Texas M.D. Anderson Cancer Center from an Indiana University School of Medicine through a Recruitment of Established Investigators Award. She has a strong history of successful extramural funding, with continuous NIH support since 1993.

Throughout her career, Dr. Guise has made seminal contributions to our understanding of cancer effects on the musculoskeletal system, beginning with demonstrating the central role for tumor–secreted PTHrP, and its downstream mediator, RANKL, in osteolytic bone metastases. These studies were the first to provide the rationale for RANKL antibodies to treat bone metastases, now FDA approved for all solid tumor metastases to bone and multiple myeloma. She developed the first animal models of osteoblastic metastases that defined the causal role of endothelin-1, and described the role of bone-derived TGF Beta in promoting bone metastases of multiple solid tumors. She showed that bone microenvironment hypoxia enhanced TGF Beta signaling to promote bone metastases and identified an inhibitor of TGF Beta signaling, PMEPA1, which is regulated in prostate cancer and whose expression predicts metastases-free survival. Recently, she has shown that bone-derived TGF Beta induces oxidation of the skeletal muscle intracellular calcium release channel (ryanodine receptor) causing calcium leak & muscle weakness.

Collectively, Dr. Guise has defined the role of tumor-bone cell interactions in the bone microenvironment and the resultant systemic effects on the musculoskeletal system that have profound implications for the treatment of bone metastases and its associated muscle weakness. Dr. Guise has received multiple honors and awards in recognition of her contributions to bone research: Outstanding Investigator Award, International Bone & Calcium Institute; Fuller Albright Award, American Society Bone & Mineral Research; Komen Scholar, Susan Komen Foundation; & Paula Stern Achievement Award, American Society Bone & Mineral Research. Her recruitment will bolster our efforts to advance research and treatment of musculoskeletal complications of malignancy.

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