Photo of Elizabeth A. Eipper, Ph.D.

Elizabeth A. Eipper, Ph.D.

Professor, Department of Molecular Biology and Biophysics
Academic Office Location:
Molecular Biology and Biophysics
UConn Health
263 Farmington Avenue
Farmington, CT 06030-3401
Phone: 860-679-8898
Fax: 860-679-1885
Website(s):

Molecular Biology and Biochemistry Graduate Program

Neuroscience Graduate Program

Neuropeptide Lab

Education
DegreeInstitutionMajor
B.S.Brown UniversityPhysical Chemistry
M.S.Brown UniversityPhysical Chemistry
Ph.D.Harvard UniversityBiophysics

Post-Graduate Training
TrainingInstitutionSpecialty
FellowshipHarvard UniversityNSF Predoctoral Fellow; Biophysics, Professor Guido Guidotti, Advisor
FellowshipUniversity of OregonAnna Fuller Fund Fellow, American Cancer Society Fellow; Postdoctoral Fellow with Professor Edward Herbert

Awards
Name of Award/HonorAwarding Organization
Osborn Award for Excellence in Graduate Student TeachingUConn Health Center
Inducted into CASECASE
Watkins Professorship, Department of Chemistry Wichita State University
Janice and Rodney Reynolds Professor of Neurobiology
Merit Award DK-32949
Elizabeth Dunaway-Burham FellowDartmouth Medical School
C.H. Li Memorial Lectureship, Berkeley, CA
Merit Award DK-32949
Ernst Oppenheimer Memorial AwardEndocrine Society
Vincent Du Vigneaud Award for Peptide Research by Young Investigators.
Name & DescriptionCategoryRoleTypeScopeStart YearEnd Year
Search Committee for CCAM faculty hireAdvisory CommitteeMemberUConn HealthUniversity20122012
Review pre-proposals and actual applications for UCIG fundingResearch CommitteeMemberUConn-StorrsLocal20122012
Committee of Five, Scientific Misconduct HearingAdvisory CommitteeChairUConn-StorrsUniversity20112012
Molecular and Cellular Endocrinology (MCE) Study SectionStudy SectionMemberExternalNational20102014
Gordon Research Conference Program Committee Professional/Scientific OrganizationMemberExternalNational20102011
Proprotein Processing, Trafficking and Secretion Gordon Research Conference Professional/Scientific OrganizationSession ChairExternalNational20102011
Search Committee for new head of the MD/PhD program Advisory CommitteeMemberUConn HealthUniversity20102011
Search Committee for Assistant to Associate Dean for Research Advisory CommitteeMemberUConn HealthUniversity20102011
T1 Course development, K30 award to Dr. Anne KennyEducation CommitteeChairUConn HealthUniversity20102013
NIH, Synapses Study Section, SYN Study SectionMemberExternalNational2009
Neuroscience Graduate Program Executive Committee Education CommitteeMemberUConn HealthUniversity20092011
Neuroscience Graduate Program Training Grant, NIH Training Grant that supports 2 first and 2 second year students Education CommitteePIUConn HealthUniversity20092010
Research Recruitment Committee Research CommitteeMemberUConn HealthUniversity20092013
MMSB Faculty Search Committee – search for faculty experts in NMR Research CommitteeMemberUConn HealthUniversity20092010
Neuroscience Faculty Search Committee – search for Solomon Chair in Vision Research Research CommitteeMemberUConn HealthUniversity20092010
Pew Scholars Program in Biomedical SciencesResearch CommitteeReviewerUConn HealthUniversity20092010
SAPC Advisory CommitteeMemberUConn HealthUniversity20092010
Admissions- Ph.D. applicantsAdvisory CommitteeInterviewerUConn HealthUniversity20092013
Admissions- MD/PhD applicantsAdvisory CommitteeInterviewerUConn HealthUniversity20092013
Johns Hopkins University - Role of Copper in Human Biology - PPG, Dr. Svetlana Lutsenko, PI Advisory CommitteeBoard memberExternalNational20092013
Equipment Competition, HCRACResearch CommitteeMemberUConn HealthLocal20092013
International Regulatory Peptide Society, Scientific Committee Member Professional/Scientific OrganizationCommittee MemberExternalInternational20082013
Student Progress Committee Education CommitteeMemberUConn HealthUniversity20082013
Senior Appointments and Promotions CommitteeAdvisory CommitteealternateUConn HealthUniversity20082010
NIH, Molecular Cellular and Develop Neuroscience IRG, Cytoskeleton and Trafficking Study Section Study SectionMemberExternalState2007
Elected to Publications Committee, ASBMB Professional/Scientific OrganizationMemberExternalNational20072010
HCRACResearch CommitteeChairUConn HealthUniversity20072019
Oversight CommitteeAdvisory Committeeelected memberUConn HealthUniversity20072008
Yale University Neuroproteomics Center Advisory Board, NIDA Advisory CommitteeMemberExternalUniversity20062008
NIH, NEI Special Emphasis Review Panel for T32 Institutional Training Grants, ZEY1 VSN Advisory CommitteeMemberExternalState2005
NIMH Special Emphasis Review Panel for course proposals, Neurobiology of Disease, ZMH1-ERB-L Advisory CommitteeMemberExternalNational2005
External Advisory Board, University of Oregon Health Sciences Center, Metal Ion Regulation in Human Cells, GM-067166 Advisory CommitteeMemberExternalNational20042007
Post-tenure Review CommitteeAdvisory CommitteeChairUConn HealthUniversity2004
Compensation Appeals CommitteeAdvisory CommitteememberUConn HealthUniversity20042007
NIH, Institutional Research Training Grants Study Section Study SectionMemberExternalNational2003
Senior Appointments and Promotions Committee Advisory CommitteememberUConn HealthUniversity2003
Neuroscience Graduate ProgramEducation CommitteeDirectorUConn HealthUniversity20022004
J. Biol. Chem. Editorial BoardEditorial BoardExternalNational20012006
Scientific Advisory Committee, GCRCAdvisory CommitteeMemberUConn HealthUniversity20012003
Neuroscience Graduate Program Education CommitteeExecutive Committee MemberUConn HealthUniversity2000
Neuroscience Graduate ProgramEducation CommitteeAssistant DirectorUConn HealthUniversity20002002
Stroke and Brain and Behavior Signature Program Advisory CommitteeConsultantUConn HealthUniversity2000
Search Committee – Cell Biology and Anatomy ChairAdvisory CommitteeMemberUConn HealthUniversity19992000
3rd Gordon Conference on Hormonal and Neural Peptides Professional/Scientific OrganizationChairExternalNational1998
Cell Biology and Anatomy – Microscope Core Facility CommitteeAdvisory CommitteeMemberUConn HealthUniversity19982000
American Cancer Society Tumor Biochemistry and Endocrinology Committee Professional/Scientific OrganizationMemberExternalNational19962000
2nd Gordon Conference on Hormonal and Neural Peptides Professional/Scientific OrganizationVice ChairExternalNational1996
J. Biol. Chem. Editorial BoardEditorial BoardExternalNational19952000
American Society for Cell Biology Professional/Scientific OrganizationMemberExternalNational19932013
NIDDK, Mol Cell Endo Study Section; ad hoc many times since then, e.g. 2004, 2005, 2008, 2010 Study SectionMemberUConn HealthNational19901994
Nominating Committee, American Peptide Society Professional/Scientific OrganizationCommittee MemberExternalNational1990
Society for Neuroscience Professional/Scientific OrganizationMemberExternalNational19872013
NIDDK, Special Grants Review Subcomm. B Professional/Scientific OrganizationMemberExternalNational19861989
NIDA, Biomedical Research Review Committee Professional/Scientific OrganizationMemberExternalNational19841985
Endocrine Society Professional/Scientific OrganizationCommittee MemberExternalNational19812013
American Society of Biological Chemists and Molecular Biologists Professional/Scientific OrganizationMemberExternalNational1979
Molecular Biology of the CellProfessional/Scientific JournalReviewerExternalNational
NatureProfessional/Scientific JournalReviewerExternalNational
ScienceProfessional/Scientific JournalReviewerExternalNational
BiochemistryProfessional/Scientific JournalReviewerExternalNational
J. NeuroscienceProfessional/Scientific JournalReviewerExternalNational
Mol. EndocrinologyProfessional/Scientific JournalReviewerExternalNational
NeuronProfessional/Scientific JournalReviewerExternalNational
J. NeuroscienceProfessional/Scientific JournalReviewerExternalNational
J. Cell. Biol.Professional/Scientific JournalReviewerExternalNational
J. Cell Sci. Professional/Scientific JournalReviewerExternalNational
Am. J. Physiology Professional/Scientific JournalReviewerExternalNational
Pepper Center Advisory Committee Advisory CommitteeMemberUConn HealthUniversity

Peptides; membrane protein trafficking; cuproenzymes; neurons; pituitary peptides seem to have preceded the 'classical' transmitters as the nervous system developed - creatures like Hydra and Drosophila utilize peptides to control key developmental decisions. Beginning with our work on proopiomelanocortin and the coordinate biosynthesis of ACTH and the opioid peptide beta-endorphin, I have been fascinated with the effort that neurons and endocrine cells devote to the biosynthesis, storage and regulated secretion of peptides. As we have learned more about the specific enzymes involved in the biosynthesis of peptides, we have learned important questions to ask about how these enzymes function in cells and in the whole animal.We have focused a great deal of our effort on the process of peptide amidation. This seemingly trivial modification to the COOH-terminus of peptides often turns out to be essential for their biological activity. Hypothalamic peptides like oxytocin and vasopressin along with neuropeptides like substance P and gastrointestinal mediators like gastrin must be amidated in order to affect their target tissues. By purifying an enzyme capable of converting peptidylglycine precursors into amidated products, we were then able to clone a cDNA encoding this enzyme.To our surprise, this modification requires the sequential action of two enzymes, a monooxygenase and a lyase. The enzyme has been named PAM, short for peptidylglycine alpha-amidating monooxygenase. The monooxygenase itself is called PHM, short for peptidylglycine alpha-hydroxylating monooxygenase, and the lyase is called PAL, short for peptidyl-alpha-hydroxylglycine alpha-amidating lyase. PHM uses ascorbic acid (vitamin C) to reduce the two copper atoms that are bound to its catalytic core and molecular oxygen is the final component of the reaction. PAL also requires a metal ion, zinc, for activity. With its need for copper, zinc and ascorbate, PAM function is sensitive to genetic and environmental factors.We have expressed the bifunctional PAM protein in soluble and membrane forms and have purified milligram amounts of the two separate catalytic domains, PHM and PAL. With Dr. Mario Amzel, we were able to deduce the crystal structures for PHM and for PAL. One copper binds to the N-terminal domain of the PHM catalytic core and the other to the C-terminal domain; how both sites contribute to the reaction is not yet clear. The beta-propeller structure of PAL constrains PHM to a location near the granule membrane, with important functional implications.Along with structure function studies, our current efforts are aimed at understanding what the cells that use PAM have to do in order to provide copper to the enzyme. Copper is an extremely toxic metal and specific pumps and chaperones are used to deliver it to the proteins that need it. PAM knockout mice do not survive beyond mid-gestation; PAM heterozygous mice are viable, but exhibit increased anxiety-like behavior, an inability to thermoregulate and increased seizure sensitivity. Many of these deficits are mimicked in mildly copper-deficient wildtype mice and ameliorated by providing supplementary dietary copper to PAM heterozygous mice. We are using these animal models to understand the role of PAM in coping with copper availability and are collaborating with our clinical colleagues to see if mild copper deficiency occurs in patient populations.In addition to its catalytic domains, PAM has non-catalytic regions. In particular, the transmembrane domain and cytosolic domain of PAM need not be present for the enzyme to function. The role of these non-catalytic domains seems to be in getting PAM to the right place in the cell so that it can do its job. In particular, the cytosolic domain is essential for targeting PAM to the secretory granules of pituitary endocrine cells and for guiding PAM protein that has reached the cell surface back into secretory granules following internalization. We recently found that a gamma-secretase-like cleavage releases a soluble cytosolic domain fragment of PAM that enters the nucleus and alters gene expression. This adds a new dimension to our studies of PAM and we are in seach of the underlying mechanism.A PAM cytosolic domain interactor protein of great interest is kalirin, a member of the Dbl family of GDP/GTP exchange factors for small GTP binding proteins of the Rho sub-family. The cytosolic domain of PAM binds to the spectrin-like repeat region of kalirin. This region of Kalirin is followed by a Dbl homology or DH domain, and a PH domain. Kalirin occurs naturally in a variety of isoforms and this first DH/PH domain can be followed by a PDZ-binding motif (Kalirin-7), an SH3 motif (Kalirin-8), another DH/PH domain (Kalirin-9) or another DH/PH domain and a putative serine/threonine protein kinase (Kalirin-12). The various isoforms of kalirin are expressed at different times during development and are localized to different regions of the cell. Mice engineered to lack expression of Kalirin globally or only in pituitary corticotropes are being used to identify the major roles of Kalirin in the pituitary and in the nervous system.

Not accepting students for Lab Rotations at this time


 


Peptide Amidation and the Control of Ciliogenesis (King and Eipper Laboratories)

Cilia are essential signaling and motile organelles that play key roles in development and homeostasis.  Defects in these microtubule-based structures lead to a broad array of phenotypes (including infertility, obesity, neurological disorders, polycystic kidneys, retinal degeneration, skeletal abnormalities and many others) collectively known as ciliopathies.  The enzyme peptidylglycine alpha-amidating monoxygenase (PAM) converts glycine-extended peptides into bioactive amidated products (e.g. oxytocin and vasopressin).  Although originally thought to have co-evolved with the nervous system, we recently found that PAM has deeper evolutionary roots and has been conserved in all organisms (even unicellular ones) that build sensory cilia.  Furthermore, using amiRNA knockdown strains of the green alga Chlamydomonas (the premier model system for analysis of cilia assembly and motility) we have now demonstrated that active PAM is not only present in cilia, but is actually essential for ciliogenesis, potentially through its effects on post-Golgi trafficking.  This project will focus on using biochemical, cell biological and molecular genetic approaches to further elucidate the mechanism(s) by which PAM activity impacts on cilia assembly and function. 

Journal Articles

Book Chapters

  • Peptidylglycine alpha-Amidating Monooxygenase (PAM)
    Vishwanatha KS, Mains RE, Eipper BA Handbook of Biologically Active Peptides 2013 Jan;Chapter 244
  • Peptides
    Mains RE, Eipper BA Basic Neurochemistry 2011 Jan;423-439
  • Neuropeptides: Synthesis and storage.
    Sobota JA, Eipper BA, Mains RE Encyclopedia of Neuroscience, Vol. 6 2007 Jan;829-836
  • Peptides
    Mains RE, Eipper BA Basic Neurochemistry, 7th Edition 2006 Jan;317-332
  • Peptides
    Mains RE, Eipper BA Basic Neurochemistry 2006 Jan;317-332
  • Amidation
    Bell, J, Eipper, BA, Mains, RE Encyclopedia of Endocrine Diseases, Vol 1 2004 Jan;188-191
  • Peptide Amidation.
    Niciu MJ, Mains RE and Eipper BA Encyclopedia of Biological Chemistry, Vol.3 2004 Jan;226-230
  • Peptidylglycine alpha-Amidating Monooxygenase (PAM).
    Steveson,RC, Bell,J, Mains,RE, Eipper,BA John Wiley Encyclopedia of Molecular Medicine, Vol 4 2002 Jan;2438-2441
  • Proopiomelanocortin synthesis and cell-specific processing
    Mains, RE, Eipper, BA Handbook of Physiology. Section 7: The Endocrine System, Volume IV: Coping with the Environment: Neural and Endocrine Mechanisms 2000 Jan;85-101
  • Neuropeptide Precursors.
    Eipper,BA and Mains,RE Elsevier’s Encyclopedia of Neuroscience 1999 Jan;1422-1423
  • Neuropeptide precursors.
    Eipper, B.A. and Mains, R.E. The Encyclopedia of Neuroscience 1997 Jan;
  • Cellular and molecular approaches to bioactive peptide processing.
    Mains,RE, Dickerson,IM, May,V, Stoffers,DA, Ouafik,L'H, Perkins,SN, Husten,EJ, Eipper,BA Frontiers in neuroendocrinology 1990 Jan;52-89
  • Tissue-specific expression of membrance and soluble forms of peptidyl-glycine alpha-amidating monooxygenase.
    Stoffers,DA, Eipper,BA Alfred Benzon Symposium 29, Neuropeptides and their Receptors 1990 Jan;152-165
  • Alternative mRNA splicing generates multiple forms of peptidyl-glycine alpha-amidating monooxygenase in rat atrium.
    Stoffers, D A; Green, C B; Eipper, B A Proceedings of the National Academy of Sciences of the United States of America 1989 Jan;86(2):735-9
  • Cotranslational and posttranslational processing in the production of bioactive peptides.
    Eipper,BA, May,V, Cullen,EI, Sato,SM, Murthy,ASN, Mains,RE Psychopharmacology: The Third Generation of Progress 1987 Jan;386-400
  • Synthesis and secretion of ACTH, beta-endorphin, and related peptides.
    Mains,RE, Eipper,BA Neurosecretion and Brain Peptides 1981 Jan;35-47
  • Basal secretion of peptides derived from the ACTH/endorphin precursor by rat pituitary cells in culture.
    Eipper,BA, Mains,RE Brain and Pituitary Peptides 1980 Jan;12-20
  • Coordinate synthesis and release of corticotropin and endorphin.
    Mains,RE, Eipper,BA Endorphins in Mental Health Research 1978 Jan;143-156
  • Studies on the common precursor to ACTH and endorphin.
    Mains,RE, Eipper,BA Endorphins '78 1978 Jan;79-126

Reviews

  • Peptidylglycine α-amidating monooxygenase as a therapeutic target or biomarker for human diseases.
    Merkler, David J; Hawley, Aidan J; Eipper, Betty A; Mains, Richard E British journal of pharmacology 2022 Feb;
  • Neuropeptide Synthesis and Storage.
    Sobota JA, Eipper BA, Mains RE Encyc of Neurosci 2009 Jan;6829-836
  • Book Review: Posttranslational Modifications of Proteins: Expanding Nature’s Inventory by Christopher T. Walsh.
    Eipper BA Quarterly Review of Biology 2008 Jan;83403
  • Kalirin: a dual Rho guanine nucleotide exchange factor that is so much more than the sum of its many parts.
    Rabiner, Chana A; Mains, Richard E; Eipper, Betty A The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry 2005 Apr;11(2):148-60
  • Kalirin: a dual Rho GEF that’s so much more than the sum of its many parts
    Rabiner CA, Mains RE, Eipper BA The Neuroscientist 2005 Jan;11148-160
  • Regulation of olfactory neurogenesis by amidated neuropeptides.
    Hansel, D E; Eipper, B A; Ronnett, G V Journal of neuroscience research 2001 Oct;66(1):1-7
  • Peptidylglycine alpha-amidating monooxygenase: a multifunctional protein with catalytic, processing and routing domains.
    Eipper,BA, Milgram,SL, Husten,EJ, Yun,H-Y, Mains,RE Prot Sci 1993 Jan;2489-497
  • The biosynthesis of neuropeptides: peptide alpha-amidation.
    Eipper,BA, Stoffers,DA, Mains,RE Annu Rev Neurosci 1992 Jan;1557-85
  • The role of ascorbate in the biosynthesis of neuroendocrine peptides.
    Eipper,BA, Mains,RE Am J Clin Nutr 1991 Jan;541153S-1156S
  • Peptide alpha-amidation.
    Eipper,BA, Mains,RE Annu Rev Physiol 1988 Jan;50333-344
  • Strategies for the biosynthesis of bioactive peptides.
    Mains,RE, Eipper,BA, Glembotski,CC, Dores,RM Trends Neurosci 1983 Jan;6229-235
  • Structure and biosynthesis of pro-adrenocorticotropin/endorphin and related peptides.
    Eipper, B A; Mains, R E Endocrine reviews 1980 Jan;1(1):1-27
Title or AbstractTypeSponsor/EventDate/YearLocation
Copper in the AmygdalaTalkCopper 2012, international symposium2012Alghero, Italy
The Roles of Kalirin Within and Outside of the Nervous SystemTalkUniversity of Barcelona2012Barcelona, Spain
Kalirin - Structure/FunctionTalkNeuroscience Department2012UCHC
Kalirin - spectrin repeats matterTalkMMSB Department Retreat2012
MMSB chalk talk Talk2011MMSB
Structure/Function – Peptide Amidation TalkMMSB Departmental Retreat 2010MMSB
Mixing animal models and protein structure: RhoGEFs at the PSD TalkMMSB Chalk Talk2010
Responsible Conduct in Research – for UCHC post-docs TalkOrganized by Dr. Gerry Maxwell2010UCHC