Peter C. Lucas, MD, PhD
Associate Professor of Pathology and Pediatrics
Dr. Lucas is a member of the Divisions of Molecular Genomic Pathology and Experimental Pathology. He is also a member of the Cellular and Molecular Pathology Graduate Program and the Vascular Medicine Institute (VMI).
5123 Rangos Research Building
Children's Hospital of Pittsburgh
4401 Penn Ave.
Pittsburgh, PA 15224
Office Telephone: 412-692-7608
Lab Telephone: 412-692-9093
- MD - Vanderbilt University School of Medicine, 1996
- PhD - Vanderbilt University School of Medicine, 1992
CertificationsAmerican Board of Pathology: Anatomic Pathology (1999)
- Molecular Anatomic Pathology
- Breast Surgical Pathology
Research InterestsDr. Lucas is a physician scientist, directing a laboratory that focuses on the relationship between chronic inflammation and the development of vascular, metabolic, and neoplastic diseases. Specifically, his lab focuses on the role of an NF- κB signaling pathway that is controlled by the "CBM signalosome", a complex of three proteins (CARMA, Bcl10, and MALT1). Dr. Lucas' lab originally identified this signalosome in lymphocytes, where it mediates NF- κB activation in response to antigen receptor ligation, and plays a critical role in the immune response. More recently, his group has found that an analogous signaling pathway operates outside the confines of the immune system, in epithelial and mesenchymal cells, where it promotes pro-inflammatory responses that contribute to a range of disease processes.
Dr. Lucas's lab is located in the Rangos Research Building, adjacent to the Children's Hospital of UPMC. The laboratory is a joint effort with Linda McAllister-Lucas, MD, PhD, the Chief of Pediatric Oncology.
Dr. Lucas and Dr. McAllister-Lucas are seeking talented and highly motivated graduate students, MSTP students, and post-doctoral fellows to work in all of the following areas of ongoing investigation:
- Lymphomagenesis: the laboratory studies the mechanisms by which point mutations or chromosomal translocations that disrupt the CARMA, Bcl10 or MALT1 genes promote the development of lymphoma. e.g., Science (2011) 331:468-472.
- Atherogenesis: the laboratory is investigating the ability of specific ligand-activated G protein-coupled receptors (GPCRs) to stimulate the CBM signaling pathway in vascular cells, particularly endothelial cells. Work focuses on the stimulation of receptors for thrombin and/or the vasoactive peptide Angiotensin II, and the resulting pro-inflammatory response that contributes to atherogenesis. e.g., J Biol Chem (2010) 285:41432-41442 or J Biol Chem (2010) 285:25880-25884.
- Type II diabetes: the role of the CBM signaling molecules is being explored in hepatocytes, in the context of obesity-dependent insulin resistance. Specifically, the lab is studying how specific saturated fatty acids, elevated in the setting of obesity and high-fat feeding, trigger components of the CBM signalosome and lead to inhibitory cross-talk with insulin signaling pathways. The resulting insulin resistance sets the stage for subsequent development of type II diabetes. e.g., Cell Reports (2012) 1:444-452.
- Carcinogenesis: the laboratory studies the phenomenon by which overexpression of the Angiotensin II receptor in a subset of "luminal type" breast cancers is indicative of poor prognosis. The focus is on understanding the contribution of excessive Angiotensin II-dependent CBM signaling in these cancers to an aggressive phenotype. e.g., PNAS (2009) 106:10284-10289.
Selected PublicationsView Dr. Lucas' publications on PubMed
Van Beek M, Oravecz-Wilson KI, Delekta PC, Gu S, Li X, Jin X, Apel IJ, Konkle KS, Feng Y, Teitelbaum DH, Ruland J, McAllister-Lucas LM, and Lucas PC (2012) Bcl10 links saturated fat overnutrition with hepatocellular NF- κB activation and insulin resistance. Cell Reports, 1:444-452.
Rosebeck S, Madden L, Jin X, Gu S, Apel IJ, Appert A, Hamoudi RA, Noels H, Sagaert X, Van Loo P, Baens M, Du MQ, Lucas* PC, and McAllister-Lucas* LM (2011) Cleavage of NIK by the API2-MALT1 fusion oncoprotein leads to noncanonical NF- κB activation. Science, 331:468-472.
Delekta P, Apel I, Gu S, Jin X, Siu K, Hattori Y, McAllister-Lucas LM, and Lucas PC (2010) Thrombin-dependent NF- κB Activation and Monocyte-Endothelial Adhesion are Mediated by the CARMA3/Bcl10/MALT1 Signalosome. J. Biol. Chem., 285:41432-41442.
McAllister-Lucas LM, Jin X, Gu S, Siu K, McDonnell S, Ruland J, Delekta PC, Van Beek M, and Lucas PC (2010) The CARMA3-Bcl10-MALT1 signalosome promotes Angiotensin II-dependent vascular inflammation and atherogenesis. J. Biol. Chem., 285:25880-25884.
Oravecz-Wilson KI, Philips ST, Yilmaz OH, Li L, Sitwala K, Lucas PC, Downing JR, Morrison SJ, and Ross TS (2009) Persistence of leukemia-initiating cells in a novel mouse model of Imatinib-responsive myeloid leukemia. Cancer Cell, 16:137-148.
Rhodes DR, Ateeq B, Cao Q, Tomlins SA, Mehra R, Laxman B, Kalyana-Sundaram S, Lonigro RJ, Helgeson BE, Bhojani MS, Rehemtulla A, Kleer CG, Hayes DF, Lucas PC, Varambally S, and Chinnaiyan AM (2009) AGTR1 overexpression defines a subset of breast cancer and confers sensitivity to losartan, an AGTR1 antagonist. Proc. Natl. Acad. Sci. USA, 106:10284-10289.
Else T, Trovato A, Kim AC, Wu Y, Ferguson DO, Kuick RD, Lucas PC, and Hammer GD (2009) Genetic p53 deficiency partially rescues the adreno-cortical dysplasia phenotype at the expense of increased tumorigenesis. Cancer Cell, 15:465-476.
McAllister-Lucas LM, and Lucas PC (2008) Finally, MALT1 is a protease! Nature Immunol., 9:231-233.
McAllister-Lucas LM, Ruland J, Siu K, Jin X, Gu S, Kim DSL, Kuffa P, Kohrt D, Mak TW, Nunez G, and Lucas PC (2007) CARMA3/Bcl10/MALT1-dependent NF- κB activation mediates angiotensin II-responsive inflammatory signaling in nonimmune cells. Proc. Natl. Acad. Sci. USA, 104:139-144.
Lucas PC, Kuffa P, Gu S, Kohrt D, Kim DSL, Siu K, Jin X, Swenson J, and McAllister-Lucas LM (2007) A dual role for the API2 moiety in API2-MALT1-dependent NF- κB activation; heterotypic oligomerization and TRAF2 recruitment. Oncogene, 26:5643-5654.
Lucas PC, McAllister-Lucas LM, and Nunez G (2004) NF- κB signaling in lymphocytes: a new cast of characters. J. Cell Sci., 117:31-39.
McAllister-Lucas* LM, Inohara* N, Lucas* PC, Ruland J, Benito A, Li Q, Chen S, Chen FF, Yamaoka S, Verma IM, Mak TW, and Nunez G (2001) Bimp1, a MAGUK family member linking protein kinase C activation to Bcl10-mediated NF- κB induction. J. Biol. Chem., 276: 30589-30597.
Lucas PC, Yonezumi M, Inohara N, McAllister-Lucas LM, Abazeed ME, Chen FF, Yamaoka S, Seto M, and Nunez G (2001) Bcl10 and MALT1, independent targets of chromosomal translocation in MALT lymphoma, cooperate in a novel NF- κB signaling pathway. J. Biol. Chem., 276:19012-19019.
Ross SE, Hemati N, Longo KA, Bennett CN, Lucas PC, Erickson RL, and MacDougald OA (2000) Inhibition of adipogenesis by Wnt signaling. Science, 289:950-953.