Brian P. Ceresa, Ph.D.

Education:

B.S., Chemistry, Providence College, Providence, RI, 1990.
Ph.D., Pharmacology, Vanderbilt University, Nashville, TN, 1995.
Postdoctoral Fellowship, Dept of Physiology and Biophysics, University of Iowa, Iowa City, IA 1995-1998
Postdoctoral Fellowship, Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 1998-2000

Curriculum Vitae

Current Positions:

Professor, Department of Pharmacology and Toxicology, University of Louisville School of Medicine
Member Experimental Therapeutics, James Graham Brown Cancer Center
Associate Member, Department of Ophthalmology and Visual Sciences, University of Louisville School of Medicine

Contact Information:

Clinical Translational Research Building, Room 305
University of Louisville
505 Hancock St.
Louisville, KY 40202, USA
Phone 502-852-2564

Email: brian.ceresa@louisville.edu

Research Description

The overarching goal of the Ceresa lab is to understand the molecular mechanisms that regulate signaling by the ErbB family of receptor tyrosine kinases, with a particular interest in the Epidermal Growth Factor Recetor (EGFR). ErbB receptor tyrosine kinases are growth factor receptors that communicate information from the exterior of the cell to the interior. In response to growth factors, these receptors mediate changes in cell growth, proliferation, differentiation, and migration. Under physiological conditions, this family of proteins plays important roles in developmental biology and regulating the homeostasis of epithelial tissues.  However, many cancers are characterized by the overexpression and/or hyperactivation of ErbB receptors. Understanding the molecular mechanisms that regulate the activity of these receptors has important implications in both cell biology and cancer biology.

Our laboratory uses a combination of biochemical, cell biological, and in vivo techniques to better understand how signaling by the ErbB receptors is regulated. Research projects in the laboratory can be divided into two broad areas:

1. How does the endocytic pathway regulate EGFR:effector communication.

While the basic mechanisms that govern activation of the EGFR are well understood, much less is known about how the duration, magnitude, and specificity of signaling occurs.  We hypothesize that ligand-mediated endocytosis is a key regulator.  Following activation of the receptor by a ligand, the ligand:receptor complex is internalized and progresses through the a series of intracellular compartments until the ligand:receptor complex reaches its ultimate subcellular location. Two major destinations are the lysosome for degradation and the plasma membrane to be re-stimulated, although there are other compartments as well. In this line of inestigation, we seek to isolate the active receptor are various stages of the endocytic pathway and determine whether specific signaling pathways (effectors) and cell responses (i.e. proliferation, migration) are inhibited, unchanged, or enhanced.  Using a variety of biochemical and cell biological tools, we can monitor the exact subcellular location of the ligand receptor complex and determine which signals emanate from which locations.

2. Does ligand-mediated downregulation of EGFR limit the receptor’s ability to promote tissue homeostasis?

In these studies, we are looking at proteins that negatively regulate EGFR signaling, with the long term goal of inhibiting the negative regulator to increase the magnitudue and/or duration of EGFR activity. Toward this goal, we are screening potential chemical inhibitors of these pathways.  Studies are initiated in corneal epithelial cells in tissue culture and the most promising candidates are used in murine models of corneal epithelial wound healing.

3. Does arsenic induce carcinogenesis via the EGFR signaling axis?

There is a well-established link between environmental arsenic exposure and the development of lung cancer, however the molecular mechanisms by which arsenic induces carcinogenesis are not well established. In these studies, we treat immortalized lung epithelial cells (Beas-2B cells) with physiologically relevant concentrations of arsenic. These are concentrations that have been observed in individuals that consumed drinking water with arsenic at levels above the EPA recommendations. Our goal is to determine how arsenic affects the expression and activity of the EGFR, how EGFR ligands are affected, and if there are changes in EGFR endocytic trafficking.

Literature Cited:

  1. Gosney JA, Wilkey DW, Merchant ML, Ceresa BP.  Proteomics reveals novel protein associations with early endosomes in an epidermal growth factor-dependent manner.  Journal of Biological Chemistry 2018 Apr 20;293(16):5895-908.  PMID: 29523688.  PMCID: PMC5912451.
  2. Gosney JA, Ceresa BP.  Using percoll gradient fractionation to study the endocytic trafficking of the EGFR.  Methods in Molecular Biology 2017;1652:145-58.  PMID: 27891641.
  3. Jackson NM, Ceresa BP.  EGFR-mediated apoptosis via STAT3. Experimental Cell Research 2017 Jul 1;356(1):93-103.  PMID: 28433699.  PMCID: PMC5514375.
  4. Ceresa BP, Gosney JS, Jackson NM*, Rush JS.  EGFR:Epidermal Growth Factor Receptor.  Encyclopedia of Signaling Molecules, 2nd Edition.  S. Choi, Editor; Springer; 2017.
  5. Rush JS, Bingaman DP, Chaney PG, Wax, MB, Ceresa BP.  Administration of menadione, vitamin K3, ameliorates off-target effects on corneal epithelial wound healing due to receptor tyrosine kinase inhibition.  Investigative Ophthalmology & Visual Sciences 2016 Nov 1;57(14):5864-5871. PMID: 27802516.
  6. Jackson NM,* Ceresa BP.  Protein Kinase G facilitates EGFR-mediated cell death in MDA­MB­468 cells.  Experimental Cell Research 2016 Aug 15;246(2):224-32.  PMID: 27381222.  PMCID: PMC4983479.
  7. Neves LFF, Duan J, Voelker A, Khanal A, McNally LR, Steinbach-Rankins JM, Ceresa BP.  Preparation and optimization of anionic liposomes for delivery of small peptides and cDNA to human corneal epithelial cells.  Journal of Microencapsulation 2016 Jun;33(4):391-9.  PMID: 27530524.  PMCID: PMC5033054.
  8. Parks EE, Ceresa BP.  Cell surface epidermal growth factor receptors increase Src and c-Cbl activity and receptor ubiquitylation.  Journal of Biological Chemistry 2014 Sep12;289(37):25537-45.  PMID: 25074934.  PMCID: PMC4162159.
  9. Ceresa BP.  Determining the role of RAB7 in constitutive and ligand-mediated epidermal growth factor receptor endocytic trafficking using single cell assays Rab GTPase.  Methods in Molecular Biology 2015;1298:305-17.  PMID: 25800853.
  10. Rush JS, Boeving MA, Berry WL, Ceresa BP.  Antagonizing c-Cbl enhances EGFR-dependent corneal epithelial homeostasis.  Investigative Ophthalmology & Visual Sciences 2014 Jul 1;55(8):4691-9.  PMID: 24985478.  PMCID: PMC4120408
  11. Ceresa BP, Peterson JL.  Cell and molecular biology of the epidermal growth factor receptor.  International Review of Cell and Molecular Biology 2014;313:145-78.  PMID: 25376492.
  12. Peterson JL*, Phelps ED, Doll MA,  Schaal S, Ceresa BP.  The role of endogenous epidermal growth factor receptor (EGFR) ligands in mediating corneal epithelial homeostasis.  Investigative Ophthalmology & Visual Sciences 2014 May 1;55(5):2870-80.  PMID: 24722692.  PMCID: PMC4008048
  13. Rush JS, Ceresa BP.  RAB7 and TSG101 are required for the constitutive recycling of unliganded EGFRs via distinct mechanisms.  Molecular & Cellular Endocrinology 2013 Dec 5;381(1-2):188-97.  PMID: 23933150.  PMCID: PMC3831653.
  14. Rush JS, Quinalty LM, Endelman L, Sherry DM, Ceresa BP.  Endosomal accumulation of the activated EGFR induces apoptosis.  Journal of Biological Chemistry 2012;287(1):712-22.  PMID: 22102283.  PMCID: PMC3249126.

PubMed Information