John J. Krolewski, M.D., Ph.D., is Professor of Pathology and Laboratory Medicine at the University of Rochester Medical Center. Dr. Krolewski is a physician-scientist whose academic interests include investigating the molecular mechanisms of cancer, and the application of clinical 'next-gen' sequencing. Dr. Krolewski received his undergraduate degree from M.I.T. and was an NIH MSTP fellow at New York University School of Medicine, receiving his M.D.-Ph.D. in 1984. He completed his pathology residency training at N.Y.U. in 1988.
Dr. Krolewski joined the faculty in the Pathology Department at Columbia University, College of P&S in 1990 and then moved to the University of California IRVINE School of Medicine in 1998, before coming to Rochester as Chair in July 2012.
He previously established Molecular Pathology clinical laboratories at both Columbia and UC Irvine and has had an NIH funded program in cancer biology since 1992. His clinical interests are focused on the application of clinical genotyping technologies, such as the use of next-generation sequencing, to assist physicians in diagnoses, and to tailor treatment to each patient's specific genotype or cancer defect. The current focus of his research program is on the mechanisms of prostate cancer cell death with a goal of translating this knowledge into novel pro-apoptotic therapies for prostate cancer.
The first part of Dr. Krolewski's career was driven by his discovery of Tyk2, the first member of the JAK family of tyrosine kinases. Working in collaboration with others, he linked Tyk2 to the interferon-alpha receptor, helped characterize the mechanism of 'broken receptor' signaling, and also the role of intra-membrane proteolysis in interferon signaling.
Subsequently, he re-focused his interests on the mechanisms of androgen withdrawal induced apoptosis of prostate epithelial cancer cells, with an emphasis on the role of cytokine signaling downstream of androgens. He has been investigating androgen regulation of the caspase inhibitor FLIP (CFLAR) and a paracrine cytokine network (TNF, TGFß) that is responsible for triggering epithelial cell death. Understanding this mechanism may enable the development of novel nanoparticle therapies for prostate cancer (currently under development with Y. Kwon, UC Irvine). He has collaborated with imaging scientists to develop and employ small animal MRI to measure prostate volume enabling his group to use KO mice to demonstrate that androgen withdrawal induced apoptosis requires TNF and TGFß signaling. He is currently participating in a multi-disciplinary collaboration (radiology, imaging physics, optics, electrical engineering, chemistry) to develop molecular imaging probes for photoacoustic imaging of early prostate cancer. He has other ongoing collaborations to develop microfluidic devices for SDS-PAGE (M. Bachman, G.P. Li, UC Irvine).
Dr, Krolewski's research has been continuously funded by the National Cancer Institute since 1992, in addition to other agencies (DOD, National Multiple Sclerosis Society, CA Dept of Health Sciences and the University of CA).
Pioli PD, Saleh AM, El Fiky A, Nastiuk KL, Krolewski JJ. "Sequential proteolytic processing of an interferon-alpha receptor subunit by TNF-alpha converting enzyme and presenilins." Journal of interferon & cytokine research : the official journal
of the International Society for Interferon and Cytokine Research. 2012 Jul 0; 32(7):312-25. Epub 2012 Mar 29.
Davis JS, Nastiuk KL, Krolewski JJ. "TNF is necessary for castration-induced prostate regression, whereas TRAIL and FasL are dispensable." Molecular endocrinology (Baltimore, Md.). 2011 Apr 0; 25(4):611-20. Epub 2011 Feb 03.
2009 Feb 15
Yoo KS, Nastiuk KL, Krolewski JJ. "Transforming growth factor beta1 induces apoptosis by suppressing FLICE-like inhibitory protein in DU145 prostate epithelial cells." International journal of cancer. Journal international du
cancer. 2009 Feb 15; 124(4):834-42.
Nastiuk KL, Krolewski JJ. "FLIP-ping out: death receptor signaling in the prostate." Cancer biology & therapy. 2008 Aug 0; 7(8):1171-9. Epub 2008 Aug 01.
2008 Jul 24
Cornforth AN, Davis JS, Khanifar E, Nastiuk KL, Krolewski JJ. "FOXO3a mediates the androgen-dependent regulation of FLIP and contributes to TRAIL-induced apoptosis of LNCaP cells." Oncogene. 2008 Jul 24; 27(32):4422-33. Epub 2008 Apr 07.