Mikhail Kolonin, Ph.D.
Director, Center For Metabolic and Degenerative Diseases
Annie and Bob Graham Distinguished Chair in Stem Cell Biology
Dr. Mikhail Kolonin, received his B.S./M.S. degree from Novosibirsk State University (Russia) and Ph.D. from Wayne State University (Detroit, MI) where he has pioneered the concept of expressing small peptides designed to disrupt specific protein interactions in live animals using Drosophila as a model. As a post-doctoral fellow at M.D. Anderson Cancer Center, he has optimized in vivo phage display technology to isolate differentially expressed vascular cell surface molecules by integrating molecular biology of angiogenesis with bioinformatics. This work, first initiated in the mouse model and then translated to screens in cancer patients, has led to several tissue-specific cell surface protein interactions that are now pursued as therapy targets. A drug prototype based on a peptide targeting interleukin-11 receptor in the prostate is in clinical trials. Based on peptide-directed drug delivery, Dr. Kolonin also co-invented an approach to obesity reversal through directed ablation of white fat vasculature. A compound targeting prohibitin protein on the surface of adipose endothelium (Adipotide), currently under commercial development, has proven effective as an experimental obesity drug in rodent and non-human primate models.
Research in the Kolonin Laboratory converges on stem cells, obesity, and cancer. Specifically, the focus is on intercellular interactions in adipose tissues and tumors and the role of adult progenitor cells in pathology. These studies are based on the analysis of clinical specimens and mouse models. Dr. Kolonin and colleagues have discovered the phenomenon of adipose cell mobilization and trafficking to tumors and the stimulatory effect of adipose stromal cells on cancer progression. These findings have provided new insights on the association between obesity and cancer. The molecular mechanisms of adipose cell migration to tumors and their role in tumor microenvironment are under investigation. The group expertise in cell population separation and identification of tissue-specific cell surface receptors has led to the recent identification of delta-decorin as the first known marker selectively expressed on adipose progenitor cells. An agent designed to target adipose progenitor cells through binding to delta-decorin is being pre-clinically tested for long-term treatment of obesity and a combination cancer therapy. Other projects are focused on identification of molecules targeting brown adipose tissue for whole body imaging applications, adipose tissue engineering in three-dimensional culture, identification of liposarcoma-initiating cells, and exploring the role of adipose tissue in leukemia progression.
Kolonin M.G., and Finley R. L., Jr. Targeting cyclin-dependent kinases in Drosophila with peptide aptamers. Proceedings of the National Academy of Sciences, USA. 95, 14266-71, 1998.
Kolonin M.G., and Finley R.L., Jr. A Role for Cyclin J in the Rapid Nuclear Division Cycles of Early Drosophila Embryogenesis. Developmental Biology. 227, 661-672, 2000.
Kolonin M.G., Zhong J., and Finley, R.L., Jr. Interaction matting methods in two-hybrid systems. Methods in Enzymology. 328, 26-46, 2000.
Kolonin M.G., Pasqualini R., and Arap W. Molecular addresses in blood vessels as targets for therapy. Current Opinions in Chemical Biology. 5, 308-313, 2001.
Arap W., Kolonin M.G., et al. and R. Pasqualini Steps toward mapping the human vasculature by phage display. Nature Medicine. 8, 121-7, 2002.
Kolonin M. G., Arap W. and Pasqualini R. Teratogenicity induced by targeting a placental immunoglobulin transporter. Proceedings of the National Academy of Sciences, USA. 99 (20):13055-60, 2002.
Kolonin M.G., Saha P. K., Chan L., Pasqualini R., Arap W. Reversal of obesity by targeted ablation of adipose tissue. Nature Medicine. 10, 625-32, 2004.
Kolonin M.G. et al. and Pasqualini R. Ligand-directed surface profiling of human cancer cells with combinatorial peptide libraries. Cancer Research. 66, 34-40, 2006.
Kolonin M.G. et al. and Arap W. Synchronous selection of homing peptides for multiple tissues by in vivo phage display. FASEB Journal. 20 (7), 979-981, 2006.
Kolonin M.G.*, Sergeeva A.*, Molldrem J., Pasqualini R., and Arap W. Display technologies: application for the discovery of drug and gene delivery agents Advanced Drug Delivery Reviews. 58, 1622-1654, 2006 (*Equal contribution).
Traktuev D., Merfeld-Clauss S., Li J., Kolonin M.G., Arap W., Pasqualini R., Johnstone B.H. and March K.L. A population of CD34-positive adipose stromal cells share pericyte and mesenchymal surface markers, reside in a perivascular niche, and stabilize endothelial networks. Circulation Research. 102, 77-85, 2008.
Cardo-Vila M., Zurita A.J., Giordano R. J., Sun J., Rangel R., Guzman-Rojas L., Anobom C.D., Valente A.P., Almeida F., Lahdenranta J., Kolonin M.G., Arap W. and Pasqualini R. A ligand peptide motif selected from a cancer patient is a receptor-interacting site within human interleukin-11, PLoS ONE. 3 (10) 3452-2460, 2008.
Nie J., Chang B., Traktuev D., Sun J., March K.L., Chan L., Sage E.H., Pasqualini R., Arap W. and Kolonin M.G. Integrin α5/β1 is a receptor for the matricellular protein SPARC on adipose stromal cells and a prospective therapeutic target, Stem Cells. 26 (10), 2735-2745, 2008.
Zhang Y, Daquinag A., Traktuev D., Amaya F., Simmons P. J., March K.L., Pasqualini R., Arap W. and Kolonin M. G. Mouse white adipose tissue is a source of cells that are recruited by tumors and promote cancer progression, Cancer Research. 15 (69) 5259-5266, 2009.
Kolonin M.G. and Simmons P.J. Combinatorial stem cell mobilization, Nature Biotechnology. 27 (3) 252-253, 2009.
Zhang Y., Bellows C.F., and Kolonin M.G. Adipose-tissue derived progenitor cells and cancer, World Journal of Stem Cells (Topic Highlight). 2 (5): 103-113, 2010.
Bellows C.F., Zhang Y., Simmons P.J., Khalsa A. and Kolonin M.G. Influence of BMI on Level of Circulating Progenitor Cells, Obesity. 19 (8):1722-1726, 2011.
Daquinag A., Zhang Y., Amaya F., Simmons P. and Kolonin M.G. An Isoform of Decorin is a Resistin Receptor on the Surface of Adipose Progenitor Cells, Cell Stem Cell. 9 (1):74-86, 2011.
Bellows C.F., Zhang Y., Chen J., Frazier M.L. and Kolonin M.G. Circulation of Progenitor Cells in Obese and Lean Colorectal Cancer Patients, Cancer Epidemiology Biomarkers & Prevention. 20 (11): 2461-2468, 2011.
Kolonin M.G.* Staquicini F. I.*, Cardó-Vila M.*, et al. and Arap W. Ligand-receptor vascular systems mapped by serial combinatorial selection in cancer patients. Proceedings of the National Academy of Sciences, USA. 108:18637-18642, 2011 (*Equal contribution).
Daquinag A., Zhang Y., and Kolonin M.G. Vascular targeting of adipose tissue as an anti-obesity approach, Trends in Pharmacological Sciences. 32:300-307, 2011.
Barnhart K., et al., Kolonin M.G. et al. and Pasqualini R. A peptidomimetic targeting white fat causes weight loss and improved insulin resistance in obese monkeys. Science Translational Medicine. 3:108-112, 2011.
Kolonin M.G., Evans K.W., Mani S.A., Gomer R.H. Alternative origins of stroma in normal organs and disease. Stem Cell Research. Dec 8. 8:312-323, 2012.
Klopp A.H., Zhang Y., Solley T., Amaya-Manzanares F., Marini F., Andreeff M., Debeb B., Woodward W.A., Schmandt R., Broaddus R.R., Lu K.H., Kolonin M.G. Omental adipose tissue-derived stromal cells promote vascularization and growth of endometrial tumors. Clinical Cancer Research. 18:771-782, 2012.
Guzman-Rojas L., et al., Kolonin M.G. et al. and Pasqualini R. Cooperative effects of aminopeptidase N (CD13) expressed by non-malignant and cancer cells within the tumor microenvironment. Proceedings of the National Academy of Sciences, USA, 109:1637-1642, 2012.
Adipose tissue cells, lipotransfer and cancer: A challenge for scientists, oncologists and surgeons.
Bertolini F, Lohsiriwat V, Petit JY, Kolonin MG.
Biochim Biophys Acta. 2012 Aug;1826(1):209-14. Epub 2012 Apr 21.
Treatment of obesity as a potential complementary approach to cancer therapy.
Sirin O, Kolonin MG.Drug Discov Today. 2012 May 22.
Progenitor cell mobilization from extramedullary organs.
Kolonin MG.Methods Mol Biol. 2012;904:243-52.
Adipose Tissue Engineering in Three-Dimensional Levitation Tissue Culture System Based on Magnetic Nanoparticles.
Daquinag AC, Souza GR, Kolonin MG.Tissue Eng Part C Methods. 2012
Stromal progenitor cells from endogenous adipose tissue contribute to pericytes and adipocytes that populate the tumor microenvironment.
Zhang Y, Daquinag AC, Amaya-Manzanares F, Sirin O, Tseng C, Kolonin MG.Cancer Res. 2012 Oct 15;72(20):5198-208.
Evaluation of Cell Function Upon Nanovector Internalization.
Martinez JO, Parodi A, Liu X, Kolonin MG, Ferrari M, Tasciotti E.Small. 2012
- Alexis Daquinag: postdoctoral fellow
- Olga Sirin: postdoctoral fellow
- Yan Zhang: research scientist
- Felipe Amaya-Manzanares: research associate
- Ahmad (Nasser) Salameh: postdoctoral fellow
- Chieh Tseng: graduate student
- Fernando Florez: Laboratory Technician