The main interest of my research is the understanding of Vitamin B12 or cobalamin (CBL) metabolism in sites of cellular proliferation. The increased cellular demand for CBL is secondary to its two coenzymatic functions. Methylcobalamin (MeCBL) serves as the cytoplasmic coenzyme for N5-methyl-tetrahydrofolate:homocysteine methyltransferase (methionine synthase [EC 220.127.116.11]). This enzyme complex catalyzes the formation of methionine from homocysteine, as well as the formation of tetrahydrofolate from methyltetrahydrofolate. Methionine is the precursor in the activated methyl cycle for S-adenosylmethionine, the universal methyl donor for DNA, RNA, protein, and cell membrane synthesis. Tetrahydrofolate is directly involved with the folate cycle that produces thymidylate during DNA synthesis. Adenosylcobalamin (AdCBL) is the mitochondrial coenzyme for methylmalonyl-CoA mutase (EC 18.104.22.168). This coenzyme is ultimately responsible for converting into syccinyl-CoA the amino acids methionine, threonine, isoleucine, and valine, any odd chain fatty acids, and propionyl-CoA. Subsequently, succinyl-CoA directly enters into Krebs cycle for the production of energy ATP.
Currently, I am collaborating with the University of Minnesota as well as Mayo Clinic in synthesizing new CBL analogs to diagnose and treat malignancy.
At the Cleveland Clinic, we are assessing the effects of CBL receptor upregulation and enhancement of apoptosis via CBL analogs.
I am collaborating with Moffitt Cancer Center, MD Anderson, and Mayo colleagues in imaging patients diagnosed with various malignancies with Indium-111-DTPA adenosylcobalamin.