Photo of Marc E. Lalande, Ph.D.

Marc E. Lalande, Ph.D.

Professor and Chair, Genetics and Genome Sciences
Academic Office Location:
Genetics and Genome Sciences
UConn Health
263 Farmington Avenue
Farmington, CT 06030-6403
Phone: 860-679-8350
Fax: 860-679-8345

Department of Genetics and Genome Sciences

Genetics and Developmental Biology Graduate Program

Skeletal Biology and Regeneration Graduate Program

Marc Lalande, Ph.D., holds the Physicians Health Services Chair in Genetics and Developmental Biology. He is professor and chairman of the Department of Genetics and Genome Sciences at the University of Connecticut School of Medicine. He is also Director of the University of Connecticut Stem Cell Institute and its Institute for Systems Genomics.

B.S.Laurentian UniversityPhysics
M.S.University of TorontoMedical Biophysics
Ph.D.University of TorontoMedical Biophysics

Post-Graduate Training
FellowshipChildren's Hospital and Department of Pediatrics, Harvard Medical SchoolResearch Fellow, Genetics Division

Name of Award/HonorAwarding Organization
Dr. Claudia Benton Award for Scientific ResearchAngelman Syndrome Foundation
Health Care Hero Award for Advancements in Healthcare Innovation Hartford Business Journal
Elected to the Connecticut Academy of Sciences and EngineeringConnecticut Academy of Sciences and Engineering
Name & DescriptionCategoryRoleTypeScopeStart YearEnd Year
Collaborative Research Day with Hartford Hospital and Connecticut Children’s Medical CenterAdvisory CommitteeOrganizerUConn HealthUniversity20112011
Ontario Research Excellence Round 5 Genomics Panel MeetingAdvisory CommitteeMemberExternalInternational20112011
NIH- Epigenomics of Human Health and Disease Panel ZRG1 GGG-M (50)Study SectionMemberExternalNational20112011
Angelman Syndrome Foundation Scientific Advisory CommitteeAdvisory CommitteeMemberExternalNational20112011
NIH Epigenomics of Human Health and Disease Panel ZRG1 GGG-M(51)Study SectionChair ExternalNational20112011
Site Visit Review Team for the Laboratory of Clinical and Developmental Genomics and the Program in Cellular Regulation and Metabolism, NIHAdvisory CommitteeMemberExternalNational20112011
Juvenile Diabetes Research Foundation VisitAdvisory CommitteeOrganizerUConn HealthUniversity20102010
Inaugural Symposium for 400 Farmington AvenueAdvisory CommitteeOrganizerUConn-StorrsUniversity20102010
Autism Speaks, Stage 2 Reviewer for Basic & Clinical applicationsAdvisory CommitteeMemberExternalInternational20102010
NIH Gene Genome and Genetics IRG at CSR, Distinguished Editor for RC4 Challenge GrantsAdvisory CommitteeMemberExternalNational20102010
Génome Québec - Genomics Research in Human Health - General Stream Peer Review Committee Advisory CommitteeMemberExternalInternational20102010
Autism Speaks – Traiblazer award applications Advisory Committee2010ExternalNational20102010
Angelman Syndrome Foundation Advisory CommitteeMemberExternalNational2010
Research Planning and Coordination, University of Connecticut School of Medicine Advisory CommitteeSenior Associate Dean UConn HealthUniversity2009
Canada Excellence Research Chairs program, Montreal QuébecAdvisory CommitteeMemberExternalInternational20092009
NIH Roadmap Epigenomics special emphasis panel, Bethesda MDStudy SectionMemberExternalNational20092009
Autism Speaks, Stage 2 Reviewer for Basic & Clinical applicationsAdvisory CommitteeMemberExternalNational20092009
INSERM Workshop 192 on “Human Pluripotent Stem Cells” Saint-Raphaël, FranceAdvisory CommitteeChair ExternalInternational20092009
International Rett Syndrome Foundation review panel Advisory CommitteeMemberExternalInternational2008
NIH-NIHGRI, Centers of Excellence in Genomic Research, Bethesda MDStudy SectionAd Hoc MemberExternalNational20082008
Canada Foundation for Innovation (CFI), Cellular and vascular imaging expert committee. Montreal QuébecAdvisory CommitteeChairExternalInternational20082008
Elected to the Connecticut Academy of Sciences and EngineeringProfessional/Scientific OrganizationMemberExternalState2007
NIH-NICHD, Developmental Biology SubcommitteeStudy SectionMemberExternalNational20072010
Québec Medical Genetics Network Advisory CommitteeMemberExternalInternational2007
Research Planning and Coordination, University of Connecticut School of Medicine Advisory CommitteeAssociate Dean UConn HealthUniversity20062008
Génome Québec Advisory CommitteeMemberExternalInternational2006
Research Planning and Coordination, University of Connecticut School of Medicine Advisory CommitteeAssistant Dean UConn HealthUniversity20042005
CNRS (France), ATIP Genetics committee, Paris Study SectionMemberExternalInternational20032009
Neurogenetics Journal Editorial BoardMemberExternalNational1998
CICATS Scientific Advisory Board Advisory CommitteeChairUConn HealthUniversity
University of Connecticut Health Center Research Recruitment CommitteeAdvisory CommitteeChairUConn HealthUniversity
$100M UConn Health Network Grant CommitteeAdvisory CommitteeMemberUConn HealthUniversity
Life Sciences Group Professional/Scientific OrganizationMemberUConn HealthUniversity
Raisz Gala Funds Committee (reviewed proposals)Advisory CommitteeMemberUConn HealthUniversity
Committee of 3 to review the University of Connecticut A.J. Pappanikou Center for Excellence in Developmental DisabilitiesAdvisory CommitteeMemberUConn HealthUniversity
Research CouncilAdvisory CommitteeMemberUConn HealthUniversity
Dean’s CouncilAdvisory CommitteeMemberUConn HealthUniversity
Health Center Research Advisory CouncilAdvisory CommitteeMemberUConn HealthUniversity
Cell and Genome Sciences Building at 400 Farmington Avenue, Building and Executive CommitteeAdvisory CommitteeMemberUConn HealthUniversity
L-Building Renovation, Building and Executive Committee Advisory CommitteeMemberUConn HealthUniversity
CLAC Tower Renovation, Building and Executive CommitteeAdvisory CommitteeMemberUConn HealthUniversity
JDH Expansion/Renovation Planning CommitteeAdvisory CommitteeMemberUConn HealthUniversity
Vice President/Dean Search CommitteeAdvisory CommitteeMemberUConn HealthUniversity
Vice President for Economic Development, Search CommitteeAdvisory CommitteeMemberUConn HealthUniversity
Director, Bioscience CT, Search CommitteeAdvisory CommitteeMemberUConn HealthUniversity

Dr. Lalande’s research is on the role of epigenetics in disease and development. Epigenetics refers the study of heritable changes in gene function that occur without an alteration in DNA sequence. The Lalande laboratory is focused on translational studies of human epigenetic disorders using murine models and human induced pluripotent stem (iPS) cell technology.

Angelman syndrome is a neurogenetic disorder characterized by severe mental retardation, "puppet-like" ataxic gait with jerky arm movements, seizures, EEG abnormalities, hyperactivity and bouts of inappropriate laughter. Individuals with AS lack a normal maternal copy of the gene encoding ubiquitin protein ligase E3A (UBE3A). UBE3A is transcribed only from the maternal allele in brain with the paternal copy of UBE3A being silenced due to an epigenetic phenomenon called genomic imprinting. Genes that are subject to genomic imprinting are expressed exclusively from one parental allele. This process is said to be epigenetic because it involves heritable changes in gene function that occur without a change in the sequence of DNA.

a) The role of Ube3a in the mammalian stress response. How the loss of UBE3A in brain causes AS is not clear. To study this problem, we have derived two different stable mouse cell lines with shRNA-mediated Ube3a knockdown. Knockdown of Ube3a in both NIH3T3 and P19 embryonic carcinoma cells resulted in increased resistance to both doxorubicin- and paraquat-induced cell death thus indicating that UBE3A functions to promote cell death in response to genotoxic and oxidative stress. Ectopic expression of wild type but not a mutant form of UBE3A, restored doxorubicin sensitivity to Ube3a-deficient NIH3T3 cells, suggesting that the ubiqitin ligase activity of UBE3A is essential for regulating the genotoxic cell death response. We have also generated a mouse model with a "humanized" Ube3a mutation consisting of a 2 bp deletion in the coding region. Using primary cells derived from these mice, we have observed that sensitivity to doxorubicin-mediated genotoxic stress is directly related to the levels of UBE3A protein in murine embryonic fibroblasts (MEFs) derived from mice homozygous, heterozygous and wild type for the Ube3a mutation. Given these results, we conclude that UBE3A may function in the ubiquitin stress response pathway and that the phenotypic manifestations of AS may be due, at least in part, to increased levels of free ubiquitin in the brain.

b) Induced pluripotent stem (iPS) cells models of AS. The recent discovery of genomic reprogramming of human somatic cells into induced pluripotent stem cells (iPS) offers an innovative and relevant approach to the study of human genetic and neurogenetic diseases such as Angelman syndrome. By reprogramming somatic cells from patient samples, cell lines can be isolated that self-renew indefinitely and have the potential to develop into multiple different tissue lineages. Additionally, the rapid progress of research on human embryonic stem cells (hESCs) has led to the development of sophisticated in vitro differentiation protocols that closely mimic mammalian development. We have perfected the experimental approaches for somatic cell reprogramming by introducing four reprogramming factors via retroviral vectors into dermal fibroblasts. We are deriving iPS cells from dermal fibroblasts from normal control and Angelman syndrome patients with the goal of differentiating the iPS cells to generate human Angelman syndrome neurons. Using these patient-specific fibroblasts and neurons, we are modeling the effects of specific human gene defects in vitro and studying how they influence genomic imprinting and UBE3A expression. Ultimately, the development of this technology will allow us to generate a human neuronal cell culture model of AS for testing small molecules or other potential therapies.

Not accepting lab rotation students at this time

A model of post-traumatic stress disorder in a tissue culture dish

Marc Lalande and Kristen Martins-Taylor, Department of Genetics and Developmental Biology and University of Connecticut Stem Cell Institute

Major risk factors for developing post-traumatic stress disorder (PTSD) are variants in genes active in the stress-response system and past childhood abuse. There is a significant need to understand such gene-environment effects in order to develop better treatments and preventive programs. We are investigating the epigenetic mechanisms that contribute to the predisposition to PTSD with a focus on FK506 binding protein 5 (FKBP5), an important regulator of the cortisol-glucocorticoid receptor (GR) complex and the hypothalamic-pituitary-adrenal (HPA) axis. In particular, the rs1360780 A/T allele enhances the interaction between intron 2 and the promoter and increases FKBP5 induction thus conferring risk for the development of PTSD. The C/G allele, on the other hand, has been deemed protective. Using human embryonic stem cells (hESCs) and gene editing technology, we are constructing an in vitro model of PTSD predisposition by generating hESCs that carry, respectively, the risk and protective rs1360780 alleles of FKBP5. We are generating isogenic pairs of hESCs carrying the FKBP5 risk variants via custom designed transcription activator-like effector nucleases (TALENs). The cell lines that are homozygous for the FKBP5 rs1360780 A (risk) and G (protective) alleles will be differentiated into neural progenitors (NPs) and subjected to stress by treatment with the glucorticoid receptor agonist dexamethasone. Our goal is to compare how the FKBP5 risk and protective variants alter the stress response by assaying for differences DNA methylation and post-translational chromatin modifications at the FKBP5 locus and across the genome.

Journal Articles

Book Chapters

  • Molecular Analysis of the Angelman/Prader-Willi Syndromes
    Lalande M, Wagstaff J, Knoll JHM Techniques and Applications of Genome Research 1995 Jan;69-82
  • Metaphase chromosome flow sorting and cloning rationale, approaches and applications
    Latt SA, Lalande M, Flint A, Harris P, Muller U, Donlon T, Tantravahi U, Bruns G, Kurnit D, Neve R, Kunkel L Flow Cytogenetics 1989 Jan;243-256
  • Molecular Genetics Via Flow Cytometry
    Van Dilla MA, Kamarck M, Lalande M Flow Cytometry and Sorting 1987 Jan;
  • Sorting, cloning, and analysis of specific human chromosomes
    Latt SA, Kanda N, Kunkel LM, Lalande M, Alt F, Kohl N, Bruns G, Aldridge J, Schreck R, Tantravahi U Chromosomes Today VII 1984 Jan;15-22
  • Construction, analysis, and utilization of recombinant phage libraries enriched for the human X chromosome by fluorescence activated flow sorting
    Latt SA, Kunkel LM, Tantravahi U, Aldridge J, Lalande M Banbury Report 14: Recombinant DNA Applications to Human Disease 1983 Jan;189-196
  • Contruction, analysis and utilization of recombinant phage libraries obtained using fluorescence activated flow sorting
    Latt SA, Kunkel LM, Tantravahi U, Aldridge J, Lalande M Recombinant DNA and Medical Genetics 1983 Jan;35-47




Title or AbstractTypeSponsor/EventDate/YearLocation
Animal Models and Their Value in Predicting Drug Efficacy and ToxicityTalkNew York Academy of Sciences2011New York, NY
Patient-Specific Induced Pluripotent Stem Cells for the Study of Neurological DiseasesTalkNew York Academy of Sciences2011New York, NY
Induced pluripotent stem (iPS) cell models of human neurogenetic disordersTalkDepartment of Human Genetics, McGill University2010Montreal, Canada
Induced pluripotent stem cells - Potential and reliabilityTalkSMi Stem Cells Conference 2010London UK
An in vitro model of Angelman syndrome via Induced pluripotent stem cell technologyTalkThe Genome Center and Epigenomic Group, University of California Davis2010Davis, CA
Derivation of live Angelman syndrome neurons from induced pluripotent stem (iPS) cellsTalkAngelman Scientific Symposium2010Chapel Hill, NC
Association des cytogénéticiens de langue françaisePoster2010Aix-en-Provence, France
Induced pluripotent stem cell models of Prader-Willi syndrome and other neurogenetic disordersTalk2010Washington DC
Somatic cell reprogramming to create an in vitro model of Angelman syndromeTalkEpigenetics and Cell Fate research unit (UMR7216 ) at University of Paris 2009Paris, France
In vitro models of human neurogenetic and imprinting disorders derived via induced pluripotent stem (iPS) cell technologyTalkM2 Stem Cells Lecture, Université Paris Diderot2009Paris France