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 Oncology
Director of Postdoctoral Affairs
Academic Office Location:
Medicine
UConn Health
263 Farmington Avenue
Farmington, CT 06030-3101
Phone: 860-679-8859
Email: cheinen@uchc.edu
Website(s):

Office of Postdoctoral Affairs

Center for Molecular Oncology

Molecular Biology and 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
NIH ClinGen Sequence Variant Interpretation Working GroupResearch CommitteeMemberExternalNational2015
International Society for Gastrointestinal Hereditary Tumors Variant Interpretation CommitteeResearch CommitteeExternalInternational2011
The American Society for Microbiology Professional/Scientific OrganizationMemberExternalNational2009
National Institute of General Medical Sciences Minority Biomedical Research ProgramAdvisory CommitteeAd Hoc ReviewerExternalNational2009
American Society for Biochemistry and Molecular BiologyProfessional/Scientific OrganizationExternalInternational20092018
Health Center Research Advisory CouncilAdvisory CommitteeMemberUConn HealthUniversity2009
American Association for Cancer ResearchProfessional/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  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 CRISPR/Cas9 gene targeting approaches to introduce missense mutations into the endogenous MMR gene loci. Second, we are using pluriopotent stem cells to study the mechanism of the MMR-dependent DNA damage response and how this might impact tumorigenesis. Finally, we are using human colonic organoids to study the effects of MMR mutation on colonic stem cell dynamics and response to damage.


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: Summer '19, Fall '19, Spring '20


Lab Rotation Projects
The research in my laboratory involves an array of techniques from cell biology to molecular genetics to genomics 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 MSH2 and MSH6 genes to understand the functions of mismatch repair affected during colorectal tumorigenesis. Projects include:


– Using cell culture models including human pluripotent stem cells to study the functions of mutant MSH2 and MSH6 in damage repair and response.


– Using CRISPR/Cas9 gene engineering to model patient derived missense mutations in the MMR genes in human cells


- Using embryonic stem cells and human colonic organoids to study the effect of MMR mutation on stem cell dynamics


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

Journal Articles

Reviews

Title or AbstractTypeSponsor/EventDate/YearLocation
Panel on Careers in Academia: The pathway(s) to your own labPanel DiscussionAmerican Society for Biochemistry and Molecular Biology2018ASBMB Annual Meeting - San Diego, CA
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