Dr. Li's long-term goal is to pursue a translational research program for the development of novel agents that improve the treatment of multiple myeloma and myeloma kidney. He started his research career with Ph.D. studies and postdoctoral training on peptide hormones at the molecular and immunological levels in Japan, 1990-1995. He has been conducting research on the role of pituitary adenylate cyclase-activating polypeptide (PACAP) in neuroprotection, male fertilization and immune responsiveness at Tulane University School of Medicine in New Orleans for the past twelve years.
The apparent pivotal role of cytokines in mediating myeloma cell proliferation, survival and migration to the bone marrow microenvironment prompted him to look into the potent immune modulatory effects of PACAP in multiple myeloma and myeloma kidney. Dr. Li's research has focused on the capacity of PACAP to block cytokine responses between myeloma cells and the bone marrow microenvironment and the resulting potent renoprotective effect in myeloma kidney. He found that PACAP could be a new antitumor agent that directly suppresses myeloma cell growth and indirectly affects tumor cell growth by modifying the bone marrow milieu of the multiple myeloma. His studies have also indicated that the tubular and interstitial injury of the myeloma kidney is induced by myeloma light chain-stimulated release of proinflammatory cytokines from the tubular epithelial cells. PACAP was found to potently suppress cytokine production from the renal proximal tubule cells both in vitro and in vivo.
The goal of his current research is to clarify the signal transduction pathways involved in the PACAP-induced suppression of cytokine production in human renal tubular cells and to develop appropriate methods of administration for novel agents to achieve effective prevention and treatment of progressive chronic kidney disease and acute renal failure in plasma cell dyscrasias. He plans to exploit new therapies that might enhance sensitivity or overcome resistance to novel chemotherapeutic agents or corticosteroid therapy. This is particularly important to our aging population, because the elderly are at increased risk of multiple myeloma and kidney injury progressing to end-stage disease. His research will address the pathologic significance, molecular mechanisms, and therapeutic intervention for kidney diseases in plasma cell dyscrasias-associated renal lesions.
Li M, Maderdrut JL, Lertora JJL, Batuman V. Intravenous infusion of pituitary adenylate cyclase-activating polypeptide (PACAP) in a patient with multiple myeloma and myeloma kidney. Peptides, 28(9): 1891, 2007.
Arimura A, Li M, Batuman V. Treatment of renal failure associated with multiple myeloma and other diseases by PACAP-38. Ann NY Acad Sci, 1070:1-4, 2006.
Li M, Cortez S, Arimura A. Pituitary adenylate cyclase-activating polypeptide is a potent inhibitor of the growth of light chain-secreting human multiple myeloma cells. Cancer Res, 66(17): 8796, 2006.
Arimura A, Li M, Batuman V. Potential protective action of pituitary adenylate cyclase-activating polypeptide (PACAP38) on in vitro and in vivo models of myeloma kidney injury. Blood, 107(2): 661, 2006.