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).

Office Location:
5123 Rangos Research Building
Children's Hospital of Pittsburgh
4401 Penn Ave.
Pittsburgh, PA 15224
Contact Information:
Office Telephone: 412-692-7608
Lab Telephone: 412-692-9093
Email: lucaspc@upmc.edu

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.

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 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.

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 (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.

Carcinogenesis

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.

Education

  • MD - Vanderbilt University School of Medicine, 1996
  • PhD - Vanderbilt University School of Medicine, 1992

Certifications

American Board of Pathology: Anatomic Pathology (1999)

Clinical Expertise

  • Molecular Anatomic Pathology
  • Breast Surgical Pathology

NIH Research

View Dr. Lucas' NIH RePORT on nih.gov

Selected Publications

View Dr. Lucas' publications on PubMed

  • Sharma D, Malik A, Steury MD, Lucas PC, and Parameswaran N (2015) Protective role for β-arrestin-2 in colitis through modulation of T cell activation. Inflam. Bowel Dis., in press
  • Logan GJ, Dabbs DJ, Lucas PC, Jankowitz RC, Brown DD, Clark BZ, Oesterreich S, and McAuliffe PF (2015) Molecular drivers of lobular carcinoma in situ. Breast Cancer Res., 17:76-86.
  • Nie Z, Du MQ, McAllister-Lucas LM, Lucas PC, Bailey NG, Hogaboam CM, Lim MS, and Elenitoba-Johnson KSJ (2015) Conversion of the LIMA1 tumor suppressor into an oncogenic LMO-like protein by API2-MALT1 in MALT lymphoma. Nature Commun., 6: 5908.
  • Marko L, Henke N, Park JK, Spallek B, Qadri F, Balogh A, Apel I, Oravecz-Wilson KI, Choi M, Przybyl L, Binger KJ, Haase N, Wilck N, Heuser A, Fokuhl V, Ruland J, Lucas PC, McAllister-Lucas L, Luft FC, Dechend R, and Muller DN (2014) Bcl10 mediates angiotensin II-induced cardiac damage and electrical remodeling. Hypertension, 64:1032-1039.
  • Sharma D, Packiriswamy N, Malik A, Lucas PC, and Parameswaran N (2014) Non-hematopoietic &beta-;arrestin-1 inhibits inflammation in a murine model of polymicrobial sepsis. Am. J. Pathology, 184:2297-2309.
  • Rosebeck S, Rehman AO, Apel IJ, Kohrt D, Appert A, O'Donnell MA, Ting AT, Du MQ, Baens M, Lucas PC*, and McAllister-Lucas LM* (2014) The API2-MALT1 fusion exploits TNFR pathway-associated RIP1 ubiquitination to promote oncogenic NF-κB signaling. Oncogene, 33:2520-2530. *These authors share senior authorship.