UCONN

HEALTH

Photo of Christopher D. Heinen, Ph.D.

Christopher D. Heinen, Ph.D.

Associate Professor, Department of Medicine
Investigator, Neag Comprehensive Cancer Center and Center for Molecular Medicine
Director, Graduate Program in Molecular Biology and Biochemistry
Academic Office Location:

UConn Health
263 Farmington Avenue
Farmington, CT 06030-3101
Phone: 860-679-8859
Website(s):

Colon Cancer Prevention Program

Center for Molecular Medicine

Molecular Biology & Biochemistry Graduate Program

Education
DegreeInstitutionMajor
B.S.Northwestern UniversityBiomedical Engineering
Ph.D.University of Cincinnati College of MedicineMolecular Genetics

Post-Graduate Training
TrainingInstitutionSpecialty
PostdoctoralThomas Jefferson University

Awards
Name of Award/HonorAwarding Organization
Research Scholar Award American Cancer Society
Wendy Will Case Cancer Fund Research Grant Award
Albert J. Ryan Fellowship Award, 1996-1998University of Cincinnati College of Medicine
Name & DescriptionCategoryRoleTypeScopeStart YearEnd Year
International Society for Gastrointestinal Hereditary TumorsResearch CommitteeExternalInternational2011
The American Society for Microbiology Professional/Scientific OrganizationMemberExternalNational2009
National Institute of General Medical Sciences Minority Biomedical Research ProgramAdvisory CommitteeAd Hoc ReviewerExternalNational2009
American Association for Cancer Research Professional/Scientific OrganizationMemberExternalNational2006

Colon cancer is the third most common malignancy in men and women and ranks behind only lung cancer in cancer deaths. The most common hereditary disease that predisposes patients to colorectal cancer is Lynch syndrome (LS) which stems from mutations in the mismatch repair (MMR) genes. In addition to its role in LS, flawed MMR has been implicated in 15-40% of sporadic colorectal and other extracolonic tumors indicating a more general role for MMR in tumor protection. Although many functional details of the MMR proteins have emerged, the mechanism by which flawed MMR contributes to tumorigenesis is not fully understood. Faulty MMR results in an elevated mutation rate (mutator phenotype), which has been proposed to lead to an accumulation of oncogene and tumor suppressor mutations that ultimately cause cancer. More recent work has revealed that MMR proteins play an important role in cell cycle arrest and apoptosis in response to certain DNA damaging agents. Thus, MMR mutations may affect tumorigenesis through multiple mechanisms. Our laboratory is interested in understanding what functions of the MMR system are affected during tumorigenesis.


We are addressing this broad question through a multi-pronged approach. First, we are examining how the biochemical and biophysical properties of MMR proteins are affected by cancer-associated missense mutations. Missense mutations of at least two MMR genes MSH2 and MSH6 have been linked to LS families providing a tool whereby full-length proteins with single amino acid alterations can be studied to determine how these alterations affect function. The MSH2 and MSH6 proteins form heterodimers in cells that recognize DNA lesions and initiate the repair process. Our laboratory utilizes purified human MSH2-MSH6 heterodimers in a series of in vitro biochemical and biophysical assays to learn about the normal biochemical mechanism as well as the consequences of cancer-associated mutations on this mechanism. Secondly, we are examining the cellular functions of the MMR proteins and the effects of cancer-causing missense mutations by studying how these mutant proteins perform in DNA repair, cell cycle checkpoint signaling, apoptosis signaling and other functional assays. Most recently, we have begun to characterize the function of the MMR pathway in human pluripotent stem cells and are using gene targeting approaches to introduce missense mutations into the endogenous MMR gene loci. Finally, we are interested in identifying proteins that interact with the normal MMR proteins and in determining how these interactions are affected during tumorigenesis.


See Dr. Heinen's NBC Connecticut interview on the importance of colon cancer screening on NBC Connecticut at: http://today.uchc.edu/headlines/2010/mar10/coloncancer.html

Accepting Lab Rotation Students:  Fall '16, Spring '17


Lab Rotation Projects
The research in my laboratory involves an array of techniques from biochemistry to cell biology to address the fundamental question of why mutations in DNA mismatch repair genes cause cancer. We are predominantly interested in using cancer-associated missense mutations of the hMSH2 and hMSH6 genes to understand the functions of mismatch repair affected during colorectal tumorigenesis. Projects include:


– Biochemical and biophysical characterizations of the wild-type and mutant MSH2-MSH6 heterodimers.
– Using cell culture models including human pluripotent stem cells to study the functions of mutant MSH2 and MSH6 in damage repair and response.
– Examining the pre-neoplastic colorectal lesions aberrant crypt foci for defects in mismatch repair.


Other projects available and can be discussed depending on student’s interest.

Journal Articles

Title or AbstractTypeSponsor/EventDate/YearLocation
The Mechanism of the Mismatch Repair-Dependent DNA Damage ResponseTalkSociety of Toxicology 52nd Annual Meeting2013San Antonio, TX
The Molecular Mechanism of the Mismatch Repair-Dependent DNA Damage ResponseTalkUniversity of Massachusetts Medical School2013Worcester, MA
Panel for Postdoctoral Fellows: The pathway(s) to your own labPanel DiscussionAmerican Society for Biochemistry and Molecular Biology Graduate and Postdo2013Boston, MA
The Challenge of Mismatch Repair Gene Missense Variants: How Understanding Molecular Mechanism Can HelpTalkUniversity of Vermont College of Medicine2013Burlington, VT
Human Disease as a Model for Mismatch Repair MechanismTalkEnvironmental Mutagen Society 43rd Annual Meeting2012Bellevue, Washington
The Mismatch Repair Molecular Mechanism and the Missense Variant MysteryTalkMassachusetts Institute of Technology2012Cambridge, MA
Panel for Postdoctoral Fellows: The pathway(s) to your own labPanel DiscussionAmerican Society for Biochemistry and Molecular Biology Graduate and Postdo2011Washington, D.C.
DNA Mismatch Repair Function in Human DiseaseTalkHospital Clinico San Carlos, Molecular Oncology Branch2011Madrid, Spain
The Molecular Mechanisms of Mismatch RepairTalkAmerican Society for Human Genetics Annual Meeting2010Washington, D.C.
Reverse Translational Research: What Lynch Syndrome Patients Can Teach Us About Mismatch Repair MechanismTalkPrinceton University, Department of Molecular Biology2010Princeton, NJ
The Functions of DNA Mismatch Repair Affected in Hereditary Colon CancerTalkYale University, Department of Molecular Biophysics and Biochemistry2010New Haven, CT
The Functions of DNA Mismatch Repair Affected in Hereditary Colon CancerTalkThe State University of New York at Buffalo School of Medicine and Biomedical Sciences2010Buffalo, NY
Nuclear Reorganization of Mismatch Repair Proteins in Response to DNA DamageTalkAmerican Society for Microbiology Conference on DNA Repair and Mutagenesis2009Whistler, Canada
The Mechanism of DNA Mismatch Repair: Lessons from Hereditary Non-Polyposis Colon CancerTalkLouisiana State University Health Center, Scott Cancer Center2008New Orleans, LA
Hereditary non-polyposis colon cancer and the role of DNA mismatch repair in cancerTalkWesleyan University, Molecular Biology and Biochemistry Department2008Middletown, CT