Peter C. Lucas, MD, PhD

Professor of Pathology and Pediatrics, Division of Molecular & Genomic Pathology

Dr. Lucas is a member of the Divisions of Molecular Genomic Pathology and Experimental Pathology and Vice Chair for Translational Pathology Imaging. He is also a member of the Cellular and Molecular Pathology Graduate Program and the Vascular Medicine Institute (VMI). Finally, Dr. Lucas is the Director of Pathology for NSABP/NRG Oncology, an NCI-sponsored clinical trials cooperative that conducts national and international trials in breast and colorectal cancer.


American Board of Pathology: Anatomic Pathology (1999)

Clinical Expertise

  • Molecular Anatomic Pathology
  • Breast Surgical Pathology
Education & Training
MD - Vanderbilt University School of Medicine, 1996
PhD - Vanderbilt University School of Medicine, 1992
2014 - Election to the American Society for Clinical Investigation (ASCI)
2017 - Award for Outstanding Teaching in Clinical Pathology, University of Pittsburgh Pathology Residency Program
Research Interests

Dr. 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.

Four specific projects are under active investigation. Each focuses on a distinct disease entity, but all are linked by overlapping mechanistic processes.


The laboratory studies the mechanisms by which point mutations or chromosomal translocations that disrupt the CARMA, Bcl10, or MALT1 genes promote the development of lymphoid neoplasms. In each case, mutations at the DNA level result in excessive, inappropriate NF-κB activation which underlies proliferative and pro-survival phenotypes. Efforts are underway to develop rational approaches for abrogating the effects of these mutations through a greater understanding of the CARMA, Bcl10, MALT1 signaling pathway.


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 (PAR1) and/or the vasoactive peptide Angiotensin II (AGTR1), and the resulting pro-inflammatory response that contributes to atherogenesis. We have also made the exciting discovery that the CBM signaling complex mediates alterations in endothelial permeability through a mechanism that does not involve NF-κB activation. This alteration in permeability plays an important role in vascular "leakiness" and in allowing for the influx of inflammatory cells into the vessel wall. Thus, the CBM complex promotes vascular inflammation both via NF-κB activation and via alterations in endothelial structural integrity.

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.


The laboratory studies the phenomenon by which overexpression of the Angiotensin II receptor (AGTR1) in a subset of "luminal type" breast cancers leads to poor prognosis. The focus is on understanding the contribution of excessive Angiotensin II-dependent CBM signaling in these cancers to an aggressive phenotype. Parallel projects are in development that explore the role of AGTR1 and the thrombin receptor (PAR1) in hepatocellular carcinogenesis and in the development/progression of osteosarcoma.

NIH Research

View Dr. Lucas' NIH RePORT on

Representative Publications

View Dr. Lucas' publications on PubMed

  • Lee JY, Ekambaram P, Carleton NM, Hu D, Klei LR, Cai Z, Myers MI, Hubel NE, Covic L, Agnihotri S, Krappmann D, Bornancin F, Lee AV, Oesterreich S, McAllister-Lucas LM, and Lucas PC (2022) MALT1 is a Targetable Driver of Epithelial-to-Mesenchymal Transition in Claudin-low, Triple-Negative Breast Cancer. Mol. Cancer Res., 20:373-386
  • Tutt ANJ, Garber JE, Kaufman B, Viale G, Fumagalli D, Rastogi P, Gelber RD, de Azambuja E, Fielding A, Balmaña J, Domchek SM, Gelmon KA, Hollingsworth SJ, Korde LA, Linderholm B, Bandos H, Senkus E, Suga JM, Shao Z, Pippas AW, Nowecki Z, Huzarski T, Ganz PA, Lucas PC, Baker N, Loibl S, McConnell R, Piccart M, Schmutzler R, Steger GG, Costantino JP, Arahmani A, Wolmark N, McFadden E, Karantza V, Lakhani SR, Yothers G, Campbell C, Geyer CE Jr; OlympiA Clinical Trial Steering Committee and Investigators (2021) Adjuvant Olaparib for patients with BRCA1- or BRCA2-mutated breast cancer.  New Engl. J. Med., 384:2394-2405.
  • Cheng J, Klei LR, Hubel NE, Zhang M, Schairer R, Maurer LM, Klei HB, Kang, H, Concel VJ, Delekta PC, Dang EV, Mintz MA, Baens M, Cyster JG, Parameswaran N, Thome M, Lucas PC, and McAllister-Lucas LM (2020) GRK2 suppresses lymphomagenesis by inhibiting the MALT1 proto-oncoprotein. J. Clin. Invest., 130:1036-1051
  • Abraham J, Montero AJ, Jankowitz R, Salkeni MA, Beumer JH, Kiesel BF, Piette F, Adamson LM, Nagy RJ, Lanman RB, Sperinde J, Huang W, Allegra CJ, Srinivasan A, Wang Y, Pogue-Geile KL, Lucas PC, and Jacobs SA (2019) Safety and efficacy of T-DM1 plus neratinib in patients with metastatic HER2-positive breast cancer: NSABP Foundation trial FB-10. J. Clin. Oncol., 37:2601-2609
  • Ekambaram P, Lee J-Y, Hubel NE, Hu D, Yerneni S, Campbell PG, Pollock N, Klei LR, Concel VJ, Delekta PC, Chinnaiyan AM, Tomlins SA, Rhodes DR, Priedigkeit N, Lee AV, Oesterreich S, McAllister-Lucas LM, and Lucas PC (2018) The CARMA3-Bcl10-MALT1 signalosome drives NF-κB activation and aggressive phenotype in AGTR1-positive breast cancer. Cancer Res., 78:1225-1240
  • Klei LR, Hu D, Panek R, Alfano DN, Bridwell RE, Bailey KM, Oravecz-Wilson KI, Concel VJ, Hess EM, Van Beek M, Delekta PC, Gu S, Watkins SC, Ting AT, Gough PJ, Foley KP, Bertin J, McAllister-Lucas LM, and Lucas PC (2016) MALT1 protease activation triggers acute disruption of endothelial barrier integrity via CYLD cleavage. Cell Reports, 17:221-232
  • 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.