Protein-protein interactions are central to the majority of biological processes. My research is focused on the key protein-protein interactions that regulate calcium during cardiac muscle contraction and relaxation. The release of sarcoplasmic reticulum (SR) Ca2+ and subsequent binding to troponin C allows the force-producing step of contraction as myosin heads traverse the actin filaments. Relaxation requires the active transport of Ca2+ into the SR against a 10,000 fold gradient, which in the human heart is performed mostly (70%) by sarco/endoplasmic reticulum calcium ATPase (SERCA). Not surprisingly, activation of SERCA function is a highly pursued therapeutic target for the treatment of heart failure where Ca2+ misregulation is a pathological hallmark. SERCA is an integral membrane enzyme and its function is regulated by protein-protein interactions with small single pass transmembrane peptides. In cardiomyocytes SERCA function can be activated and inhibited by protein-protein interactions with dwarf opening reading frame (DWORF) and phospholamban (PLB), respectively.
The overarching goal of my research is to establish structural models of the protein-protein interaction of SERCA/PLB and SERCA/DWORF during Ca2+ transport and to leverage our experimental models to discover novel therapeutics (peptides and small molecules) capable of enhancing SERCA’s function to pump calcium into the SR.
I am directly involved in the engineering of structure-based biosensors to assay SERCA-coupled calcium transport. These biosensors are designed with fluorescent proteins at specific loci of SERCA and PLB. Binding and domain movements are then detected by fluorescence resonance energy transfer (FRET) between the donor and acceptor fluorescent protein. The biosensor can be expressed in live cells (e.g., HEK293) and can be assayed in a native SR/ER environment. This experimental model is a powerful tool to study the binding and dynamics of the SERCA-PLB complex and can be used as a high-throughput screening FRET assay for drug discovery.
A recently discovered transmembrane peptide named DWORF (Nelson et al., 2016) activates SERCA by displacing the endogenous SERCA inhibitors (e.g., PLB). We are currently developing spectroscopic tools to better understand these key protein-protein interactions
University of Minnesota-Twin Cities, Minneapolis, MN
Biochemistry, Molecular Biology, and Biophysics PhD program
University of San Diego, San Diego, CA
Bachelor of Arts in Biochemistry
2012 - 2017 University of Minnesota-Twin Cities, BMBB Department, Minneapolis, MN. Graduate Research Assistant Advisor: David D. Thomas, Ph.D.
2008 - 2010 Vertex Pharmaceuticals, DMPK Department, San Diego, CA. Bioanalytical Research Associate Supervisor: Yongmin Li, Ph.D.
2007 - 2008 University of San Diego, Chemistry Department, San Diego, CA. Research Assistant Advisor: David De Haan, Ph.D.
Chaudhury I., Stroik D.R., Sobeck A. 2014. FANCD2-Controlled Chromatin Access of the Fanconi-Associated Nuclease FAN1 is Crucial for the Recovery of Stalled Replications Forks. Mol. Cell. Biol. 34(21): 3939-54.
De Haan D.O., Corrigan A.L., Smith K.W., Stroik D.R., Turley J.J., Lee F.E., Tolbert M.A., Jimenez J.L., Corodova K.E., Ferrell G.R. 2009. Secondary organic aerosol-forming reactions of glyoxal with amino acids. Environ. Sci. Technol. 43: 2818-24.
Poster and Oral Presentations
Keystone Symposium: Engineered Cells as Platforms for Discovery, Boston, MA
Presented new results on assay development / validation and drug screening on a structure-based fluorescent sensor for SERCA-coupled calcium transport. Levofloxacin and Sulindac are novel compounds that modulate SERCA-PLB complex.
Biophysical Society Meeting, Los Angeles, CA; New Orleans, LA
Presented work on a live-cell inducible system expressing GFP-SERCA and RFP-PLB and demonstrated that the binding and structural states of SERCA/PLB can be resolved by TR-FRET.
Biomedical Sciences Graduate Programs Research, Minneapolis, MN
Presented new results showing that high calcium remodels the binding interface of SERCA-PLB in permeabilized HEK293 cells.
BMBB Department Research Seminar Series, Minneapolis, MN
Annual departmental seminar on recent research and results attended by graduate students, post-docs, professors, and researchers.
Keystone Symposium: Genomic Instability and DNA Repair, Whistler, BC
Presented work demonstrating a novel function for Fanconi Anemia proteins FANCD2 and FAN1 at the replication fork.
American Association of Pharmaceutical Scientists Annual Meeting, Los Angeles, CA
Presented data on recently developed high-throughput HPLC-MS/MS microsomal stability assay to report drug metabolism and pharmacokinetics.
American Chemical Society Western Regional Meeting, San Diego, CA
Presented new results on reaction kinetics of glyoxal with five amino acids common in atmosphere measured by NMR, AMS, and ESI-MS.
Awards and Honors
Hogenkamp Award in Enzymology, University of Minnesota, Minneapolis, MN
Awarded annually to graduate students with excellent research emphasizing on enzymology; in recognition of the careers of emeritus faculty member, Harry Hogenkamp.
Cyrus Barnum Teaching Award, University of Minnesota, Minneapolis, MN
Award given to graduate students in the name of Cyrus Barnum in recognition of excellence in teaching.
BMBB Travel Award, University of Minnesota, Minneapolis, MN
Travel support to share research findings, form collaborations, and get up-to-date on latest research and methodology at the Keystone Symposia: Engineered Cells in Boston.
Charles Carr / William Peterson Award, University of Minnesota, Minneapolis, MN
Awarded annually to graduate students with excellent research emphasizing on metabolism and regulation; in recognition of the careers of BMBB emeritus faculty member, Charles Carr and his student William Peterson.
Graduate Student Leadership Award, University of Minnesota, Minneapolis, MN
Given to graduate student representatives in recognition of their work ensuring student views on meetings, recruiting, and other issues.
Dean’s List, University of San Diego, San Diego, CA
Top 10% of the class in GPA
Choral Scholarship Award, University of San Diego, San Diego, CA
USD's Choral Scholars is a vocal ensemble composed of select students of high academic caliber and possessing exceptional vocal ability, coupled with a unique scholarship program.
California Governor’s Scholars Award, University of San Diego, San Diego, CA
The Governor's Scholars Award provides scholarships to students who demonstrated high academic achievement on exams in the Standardized Testing and Reporting (STAR) program.
Science from Scientists, Poplar Bridge Elementary, Bloomington, MN
Non-profit organization whose goal is to ensure our nation’s youth is competitive globally in STEM fields through hands-on instruction and training by practicing scientists.
Association of Multicultural Scientists, Minneapolis, MN
Student organization with an interest in fostering and supporting diversity in the biological sciences. Participated in STEM awareness events for elementary school students.
Muscular Dystrophy Association, Minneapolis, MN
Participated in fundraising events to support MDA-funded research.
University of Minnesota, BMBB Department, Minneapolis, MN
Graduate Student Representative
Elected position whose major responsibilities included serving on BMBB Graduate Program Coordinating Committee, hosting seminar speakers, and facilitating graduate student and faculty recruiting efforts.
Teaching Experience and Mentorship
University of Minnesota-Twin Cities, Minneapolis, MN
Biochemistry II: Molecular Mechanisms of Signal Transduction and Gene Instruction (BIOC4332)
Lectured on DNA Replication.
Molecular Cellular and Structural Biology Graduate Orientation (MCDG 8920).
Instructed lab module on Taq polymerase purification.
Mentorship: Harini Kethar, Skylar Fausner, Jinhua Wang
2016-2017 National Institute of Health Training Grant in Muscle Research, T32AR007612
2014-2015 National Cancer Institute Training Grant in Cancer Biology, T32913840
2015-2017 Biophysical Society