Kevin P. Claffey, Ph.D.Professor, Department of Cell Biology
Center for Vascular Biology
- Education & Training
- Committees & Organizations
- Research Opportunities
- Lab Rotations
|B.A.||Western Connecticut State University||Biochemistry|
|Ph.D.||Boston University||Biochem & Mol. Biology|
|Postdoctoral||Department of Cellular and Molecular Biology,(Dana-Farber Cancer Institute) and Department of Biological Chemistry and Molecular Pharmacology, (Harvard Medical School)||Postdoctoral Research Fellow, Mentor: Dr. Bruce Spiegleman|
|Name of Award/Honor||Awarding Organization|
|Dean of Arts and Sciences 2011 Alumni Award||Western Connecticut State University|
|Diversity Awareness Certificate||University of Connecticut Health Center|
|Improving Managerial skills of the New and Prospective Manager||American Management Association|
|Beth Israel and Science Teacher Educational Partnership Certificate of Appreciation||Beth Israel Deaconess Medical Center|
|National Research Service Award, Title: Identification of Genes Regulated in Adipose Differentiation, 1988-1991||NIH-NIDDK|
|Student Achievement Award||American Chemical Society|
|Biochemistry Training Grant, 1984-1988||Boston University School of Medicine|
|Name & Description||Category||Role||Type||Scope||Start Year||End Year|
|Animal Care and Use Committee||Professional/Scientific Organization||Member||UConn Health||University||2021||2024|
|Reviewer Komen CT Breast Cancer Foundation||Study Section||Reviewer||External||Regional||2016||2020|
|UCH Molecular Core Facility||Other||Director||UConn Health||University||2016||2020|
|UCHC AAUP President and Chief Negotiator||Other||Chief Negotiator||UConn Health||University||2012||2020|
|Graduate Program Student Advisor (2)||Advisory Committee||UConn Health||University||2010||2020|
|IRB Scientific Review Committee||Research Committee||Member||UConn Health||University||2009||2020|
|Health Center Research Advisory Committtee||Advisory Committee||Member||UConn Health||University||2009||2020|
|Breast Cancer Alliance Scientific Review Cmt||Research Committee||Member||External||Regional||2009||2020|
|Neage Cancer Center - ACS Review||Study Section||Member||UConn Health||University||2008|
|American Heart Association, Northeast Region 5B||Study Section||Member||External||National||2008|
|NIH-NCI, Innovative Methods of Analysis Technologies – Study Sections||Study Section||Member||External||National||2005||2018|
|Clinical and Translational Breast Cancer Program, NEAG Comprehensive Cancer Center||Advisory Committee||Co-Director||UConn Health||University||2005||2018|
|American Heart Association||Study Section||Member||External||National||2004||2009|
|NIH-NCI, Tumor Microenvironment, Ad Hoc Study Sections||Study Section||Member||External||National||2003||2005|
|Dental Council||Education Committee||Member||UConn Health||University||2002||2004|
|Summer Undergraduate Research Fellowship Program||Education Committee||Coordinator||External||University||2002||2009|
|UCHC Institutional Tumor Bank Development Committee||Professional/Scientific Organization||Member||UConn Health||University||2002|
|NIH-NCI, Site Visit and Program Project Study Sections for Angiogenic Program and Tumor Biology PO1 Grants||Study Section||Member||External||National||2002||2004|
|Biorepository Advisory Cmt.||Advisory Committee||Member||UConn Health||University||2002|
|NIH-SSS-N, OGR, Special Ad-Hoc Study Section, Post-Doctoral NRSA Fellowships||Study Section||Member||External||National||2001||2003|
|Tobacco-Related Disease Research Program, Univ. of California||Study Section||Member||External||University||2001||2019|
|UCHC Research Histology Core Facility||Other||Director||UConn Health||University||1999||2019|
|American Heart Association, Northeast Region 5B||Study Section||Member||External||National||1999||2002|
|American Association for Cancer Research||Professional/Scientific Organization||Member||External||International||1996||2019|
|Animal Care and Research Committee, Beth Israel Deaconess Medical Center||Research Committee||Member||External||Regional||1995||1998|
|Research Computing Committee, Beth Israel Deaconess Medical Center||Research Committee||Member||External||Regional||1994||1995|
|American Society for Investigative Pathology||Professional/Scientific Organization||Member||External||International||1992||2018|
The projects in Dr. Claffey's laboratory are focused on pre-clinical models of breast cancer, particularly targeting angiogenesis and VEGF-dependent mechanisms is a key area of interest for my laboratory. Key areas of expertise include both real-time animal imaging and post-analysis using quantitative histological and biochemical methods. Dynamic vascular events such as induced permeability, local endothelial cell apoptosis and analysis of vascular flow are all important aspects of tumor angiogenesis and multiple cardiovascular diseases. Identification of a potential therapeutic target for pathological excess vascular permeability is a most recent breakthrough. Translational research in breast cancer includes local lymph node immune responses to cancer antigens and recovery of patient-specific anti-cancer antibodies.
Post-Doctoral Candidates with relevant experience will be considered. Please submit a CV or Biosketch with contact information for at least three references to:firstname.lastname@example.org.
Accepting Lab Rotation Students: Fall 2022 and Spring 2023
Lab Rotation Projects
1. Therapeutic Targeting of Breast Cancer Dormancy, Resistance and Stem Cell Mechanisms. A new project in the lab that targets the cancer stem cell phenotype and dormant metastatic breast cancer. The current approach blocks the effect of detoxification pathways which promote cell survival in metastatic sites during chemotherapy treatment. The “unblocking” this protection pathway with unique therapeutic compounds will significantly improve therapeutic targeting of distal metastatic disease to prevent recurrence. Project involves the testing of various unique compounds using in vitro breast cancer cell models as well as translating effective compounds into animal pre-clinical models of primary and metastatic disease.
2. Breast Cancer Initiation and Progression through the Epigenetic Suppression of Key Metabolic and Signaling Pathways. Our long-standing interest in stress responses that are overridden in cancer have evolved into defining early events that define breast cancer risk and promote progression. One key pathway is the activation of the AMP-dependent kinases (AMPK) under metabolic stress. The catalytic isoform AMPKa2 appears to be crucial to suppression of proliferation signals and has been shown to be epigenetically suppressed in early human breast cancer. We are currently testing models of cancer cells deficient in AMPKa2 by RNA interference in vitro, long-term suppression using in vivo models and genetic deletion in endogenous animal cancers. The suppression of this pathway and its contribution to breast tumorigenesis and metastasis indicates the importance of normal growth control. The main project relates to genetic animal models and in vivo tumor growth and metastasis of cells with modified levels of AMPKa2 expression.
3. Isolation of Patient-Derived Anti-Cancer Antibodies from Tumor Draining Sentinel Lymph Nodes in Breast Cancer and Melanoma. A novel methodology has been developed in the lab to investigate whether patients have a strong immune response to cancer antigens within tumor-draining lymph nodes. We have taken tumor draining lymph nodes from patients and identified B-cell activation within the node, isolated complete cDNA libraries for the antibodies being synthesized there, and used recombinant antibodies to identified novel tumor antigens. A novel methodology is being tested to identify antibodies from live cells and produce antibody clones within a week of sentinel lymph node sampling. These antibodies will be developed for primary biomarker diagnostics using multiplex assays and as a therapeutic option for late stage metastatic cancers.
PLC (Phospholipase C) β2 Promotes VEGF (Vascular Endothelial Growth Factor)-Induced Vascular Permeability.
Arteriosclerosis, thrombosis, and vascular biology 2022 Jul;101161ATVBAHA122317645
Label-Free Morphological Phenotyping of In Vitro 3D Microtumors.
Methods in molecular biology (Clifton, N.J.) 2022 Jan;239431-46
GRK2 enforces androgen receptor dependence in the prostate and prostate tumors.
Oncogene 2020 Jan;
Elastography of multicellular spheroids using 3D light microscopy.
Biomedical optics express 2019 May;10(5):2409-2418
Overcoming hypoxia-induced chemoresistance to cisplatin through tumor oxygenation monitored by optical imaging.
Nanotheranostics 2019 Jan;3(2):223-235
Contribution of three-dimensional architecture and tumor-associated fibroblasts to hepcidin regulation in breast cancer.
Oncogene 2018 Apr;374013-4032
A RAS-CaMKKβ-AMPKα2 pathway promotes senescence by licensing post-translational activation of C/EBPβ through a novel 3'UTR mechanism.
Oncogene 2018 Mar;373528-3548
Stiffness analysis of 3D spheroids using microtweezers.
PloS one 2017 Jan;12(11):e0188346
AMPKα Is Suppressed in Bladder Cancer through Macrophage-Mediated Mechanisms.
Translational oncology 2016 Dec;9(6):606-616
AMPKalpha2 Regulates Bladder Cancer Growth Through SKP2-mediated Degradation of p27.
Molecular cancer research : MCR 2016 Sep;141182-1194
Descriptive analysis of tumor cells with stem like phenotypes in metastatic and benign adrenal tumors.
Journal of pediatric surgery 2015 Sep;50(9):1493-501
Inhibition of breast cancer cell migration by activation of cAMP signaling.
Breast cancer research and treatment 2015 May;152(1):17-28
Cardiomyopathy and Worsened Ischemic Heart Failure in SM22-α Cre-Mediated Neuropilin-1 Null Mice: Dysregulation of PGC1α and Mitochondrial Homeostasis.
Arteriosclerosis, thrombosis, and vascular biology 2015 Apr;35(6):1401-12
Increased expression of L-selectin (CD62L) in high-grade urothelial carcinoma: A potential marker for metastatic disease.
Urologic oncology 2015 Jan;33(9):387.e17-27
Patient-derived heavy chain antibody targets cell surface HSP90 on breast tumors.
BMC cancer 2015 Jan;15614
Expression of phosphodiesterase 6 (PDE6) in human breast cancer cells.
SpringerPlus 2013 Dec;2680
AMP-Activated Protein Kinase α 2 Isoform Suppression in Primary Breast Cancer Alters AMPK Growth Control and Apoptotic Signaling.
Genes & cancer 2013 Jan;4(1-2):3-14
Hypoxia-induced response of cell cycle and apoptosis regulators in melanoma.
International journal of dermatology 2012 Oct;51(10):1263-7
Revealing the role of phospholipase Cβ3 in the regulation of VEGF-induced vascular permeability.
Blood 2012 Sep;120(11):2167-73
Prostate specific membrane antigen (PSMA) regulates angiogenesis independently of VEGF during ocular neovascularization.
PloS one 2012 Jul;7(7):e41285
Prolonged mammosphere culture of MCF-7 cells induces an EMT and repression of the estrogen receptor by microRNAs.
Breast cancer research and treatment 2012 Feb;132(1):75-85
AMPKα2 Suppresses Murine Embryonic Fibroblast Transformation and Tumorigenesis.
Genes & cancer 2012 Jan;3(1):51-62
Symptom distress associated with biopsy in women with suspect breast lesions.
ISRN oncology 2012 Jan;2012898327
Imaging tumor hypoxia by near-infrared fluorescence tomography.
Journal of biomedical optics 2011 Jun;16(6):066009
Genomic differences between estrogen receptor (ER)-positive and ER-negative human breast carcinoma identified by single nucleotide polymorphism array comparative genome hybridization analysis.
Cancer 2011 May;117(10):2024-34
Proteins that bind the Src homology 3 domain of CrkI have distinct roles in Crk transformation.
Oncogene 2010 Dec;29(48):6378-89
Dietary energy availability affects primary and metastatic breast cancer and metformin efficacy.
Breast cancer research and treatment 2010 Sep;123(2):333-44
Differential protein expression profiles in estrogen receptor-positive and -negative breast cancer tissues using label-free quantitative proteomics.
Genes & cancer 2010 Mar;1(3):251-71
Identification of novel tumor antigens with patient-derived immune-selected antibodies.
Cancer immunology, immunotherapy : CII 2009 Feb;58(2):221-34
Argonaute-2 expression is regulated by epidermal growth factor receptor and mitogen-activated protein kinase signaling and correlates with a transformed phenotype in breast cancer cells.
Endocrinology 2009 Jan;150(1):14-23
Therapeutic metformin/AMPK activation promotes the angiogenic phenotype in the ERalpha negative MDA-MB-435 breast cancer model.
Breast cancer research and treatment 2009 Jan;113(1):101-11
AMP-dependent protein kinase alpha 2 isoform promotes hypoxia-induced VEGF expression in human glioblastoma.
Glia 2006 May;53(7):733-43
Hypoxia stimulates breast carcinoma cell invasion through MT1-MMP and MMP-2 activation.
Oncogene 2006 Apr;25(16):2379-92
N-acetyl-cysteine promotes angiostatin production and vascular collapse in an orthotopic model of breast cancer.
The American journal of pathology 2004 May;164(5):1683-96
Induction of tumor lymphangiogenesis by VEGF-C promotes breast cancer metastasis.
Nature medicine 2001 Feb;7(2):192-8
Regulation of human vascular endothelial growth factor mRNA stability in hypoxia by heterogeneous nuclear ribonucleoprotein L.
The Journal of biological chemistry 1999 Jan;274(3):1359-65
Hypoxia-mediated regulation of gene expression in mammalian cells.
International journal of experimental pathology 1998 Dec;79(6):347-57
Identification of a human VPF/VEGF 3' untranslated region mediating hypoxia-induced mRNA stability.
Molecular biology of the cell 1998 Feb;9(2):469-81
Hypoxia regulates the expression of vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) and its receptors in human skin.
The Journal of investigative dermatology 1997 Mar;108(3):263-8
Expression of vascular permeability factor/vascular endothelial growth factor by melanoma cells increases tumor growth, angiogenesis, and experimental metastasis.
Cancer research 1996 Jan;56(1):172-81
Structural requirements for dimerization, glycosylation, secretion, and biological function of VPF/VEGF.
Biochimica et biophysica acta 1995 Jan;1246(1):1-9
Vascular endothelial growth factor. Regulation by cell differentiation and activated second messenger pathways.
The Journal of biological chemistry 1992 Aug;267(23):16317-22
Academic LIMS: Automated determination of calcium in human serum by atomic absorption spectroscopy
Amer Lab 1992 Jan;2415-20
Cloning and tissue distribution of rat heart fatty acid binding protein mRNA: identical forms in heart and skeletal muscle.
Biochemistry 1987 Dec;26(24):7900-4
AMPK in BCR-ABL expressing leukemias. Regulatory effects and therapeutic implications.
Oncotarget 2011 Dec;2(12):1322-8
Role of CaMKK2-AMPK signaling in breast cancer metabolic and hypoxic stress responses
SLN Antibody Libraries
The metabolic regulator AMPKa2 is a putative tumor suppressor in breast cancer
Expression of the cancer stem cell marker, ALDH1A1 in primary breast cancer: a mechanism for chemoresistance
The role of AMPKa2 as a putative tumor suppressor in breast cancer
AMPK Activity in Cancer: A Double-Edged Sword? Inhibition of Proliferation and Nutrient Stress-Induced Survival in Breast Carcinoma
AMPK Dependent c-Raf Signaling Promotes Breast Carcinoma Cell Viability in Hypoxia
Mice with a null mutation for macrophage migration inhibitory factor have lower stage tumors in a model of bladder cancer.
Taylor won New Investigator Award.
AMP-dependent Protein Kinase alpha1 and alpha2 Isoforms are Central Regulators of Hypoxia-Induced VEGF Expression
AMPK regulates hypoxia-inducible factor-1 transcriptional activation and VEGF expression in human glioblastoma
Molecular profiling of angiogenic markers: a step towards interpretive analysis of a complex biological function.
The American journal of pathology 2002 Jul;161(1):7-11
Melanoma on the move: the progression of melanoma: novel concepts with histologic correlates.
The American Journal of dermatopathology 2004 Dec;26(6):504-10
Melanoblasts on the move: Rac1 sets the pace.
Small GTPases 2004 Jan;3(2):115-9
Vascular permeability factor/vascular endothelial growth factor: a multifunctional angiogenic cytokine.
EXS 1997 Jan;79233-69
Regulation of VEGF/VPF expression in tumor cells: consequences for tumor growth and metastasis.
Cancer metastasis reviews 1996 Jun;15(2):165-76
Vascular permeability factor/vascular endothelial growth factor: an important mediator of angiogenesis in malignancy and inflammation.
International archives of allergy and immunology 1995 Jan;107(1-3):233-5
Vascular permeability factor, tumor angiogenesis and stroma generation.
Invasion & metastasis 1994 Jan;14(1-6):385-94
|Title or Abstract||Type||Sponsor/Event||Date/Year||Location|
|Patient Derived Anti-Cancer Antibodies Target Cell Surface Epitopes||Talk||2014||Merrimack Pharm. Inc.|
|Patient Derived Anti-Cancer Antibodies Target Cell Surface Epitopes||Talk||2014||Immunogen, Inc.|
|Conditional Reprogrammed Cancer Cells for Therapeutic Testing||Talk||Hanson-Wade||2013||Tumor Biology Models|
|ASIP - Molecular models of stress signaling in breast cancer||Talk||ASIP - Experimental Biology||2011||Washington DC.|
|Regulation of Breast Cancer Stem Cell Fate by MicroRNAs||Talk||Annual Meeting at Experimental Biology||2011|
|Potential and Concerns for Therapeutic AMPK Activation in Breast Cancer||Talk||Biochemistry and Molecular Biology Seminar Series||2011||Mayo Clinic, Rochester MN|
|Discovery Platform for Identifying Anti-Cancer Antibodies||Talk||BioDesign Institute||2011||Tempe AZ|
|Breast Cancer Treatment and Research||Talk||CT Breast Health Initiative||2011||WDRC FM|
|Translational Breast Cancer Research - Patient-derived antibodies for personalized medicine||Talk||UMASS Worcester||2010||Worcester, MA|
|Current Breast Cancer Treatment and Research||Talk||International Aero Engines||2010||East Hartford, CT|
|Neag Cancer Center Retreat||Talk||NEAG CC UCHC||2010||Farmington, CT|
|MEtformin as a breast cancer therapeutic AMPK activator||Poster||San Antonio Breast Cancer Symp./AACR||2010||San Antonio, TX|
|Identification of active sentinel lymph nodes in cancer patients||Talk||Clinical Melanoma Conference||2009||New Haven, CT|
|Breast Cancer and Beyond: A Conversation with the Experts||Panel Discussion||Discovery Series UCONN Health Center. Open Public Informational Series||2009||Farmington, CT|
|Identification of Patient-Derived Antibodies||Talk||Department of Cell and Molecular Biology, St. Louis University||2009||St. Louis, MI|
|Animal models of primary and metastatic breast cancer||Talk||Center for Vascular Biology, Department of Pathology, Yale School of Medicine||2008||New Haven CT|
|Identification of Breast Cancer Antigens||Talk||NIH:NCI IMAT Investigator Meeting||2007||San Francisco, CA|
|Career opportunities in the Biomedical Sciences||Talk||Region 10 Honors High School Program||2007|
|AMPK regulates Hypoxia Induced VEGF in Glioblastoma||Talk||Keystone Meeting on Hypoxia||2006||Colorado|
|Hypoxia Regulation of MT1-MMP/MMP-2 Activation in Breast Cancer Invasion and Metastasis||Talk||Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School||2002||Boston, MA|
|Orthotopic Breast Cancer Models of Tumor Growth, Invasion and Metastasis||Talk||Department of Medicine, Center for Cutaneous Biology, Mass General Hospital and Harvard Medical Scho||2001||Cambridge, MA|
|Role of Infiltrating Stromal Cell VEGF Expression in bFGF-Induced Angiogenesis||Talk||Yale School of Medicine, Department of Pathology||2000||New Haven, CT|
|Cytokine-dependent in vivo angiogenesis models||Talk||Praecis Pharmaceutical Inc||1997||Cambridge, MA|
|Hypoxia-mediated gene expression, Transcription and mRNA stability: Mechanisms for tumor cell survival||Talk||Dartmouth Medical College and Veterans Administration Medical Center, Department of Microbiology and||1997||Lebanon, NH|
|Experimental approaches to block hypoxia-induced VEGF mRNA expression in human tumor cells: models for drug discovery programs||Talk||BioChem Therapeutic||1996||Laval, Quebec|
|VEGF dependent angiogenesis models and novel approaches to anticancer drug targets||Talk||Pfizer Discovery Research Seminar||1996|
|Hypoxia-mediated gene expression, Transcription and mRNA stability; Mechanisms for tumor cell survival||Talk||Shriners Burns Institute Seminar Series||1996|
|VEGF mRNA regulation by hypoxia and correlation with experimental retinopathy models||Talk||Rassmussen Foundation Research Advances, Annual Review||1995|