Cole Dovey
Assistant Professor of Chemistry/Biochemistry
- Office
- McCardell Bicentennial Hall 447
- Tel
- (802) 443-3152
- cdovey@middlebury.edu
- Office Hours
- Spring 2024: T 2-3:30 pm, R 3:30-4:30 pm or by appointment
Research in my group aims to understand the biochemistry of cell death. Recently, different forms of regulated cell death have been identified as biochemically and morphologically distinct from apoptosis. Our focus is on necroptosis, a process orchestrated by the interaction of certain proteins, lipids, and metabolites that ultimately triggers cell lysis. It is currently unclear how these death effector molecules are activated to assemble and unleash membrane disruption. A key factor is the pseudokinase MLKL, which specifically binds to phospholipids, forms oligomers, and has membrane permeabilizing activity. Our recent work has identified an important role for inositol phosphate metabolites in activating MLKL.
Questions for ongoing research: How is the activation and assembly of MLKL, and other death effector molecules, regulated to control cell death? How do pathogens co-opt cell death pathways to their advantage? What tools might we develop to precisely control cell death to our advantage? My lab uses state-of-the-art methods in biochemistry and genetics (e.g., CRISPR, haploid human genetics, and chemical genetics) to probe these questions, and more.
Regulated necrosis is crucial for antiviral immune defense; its dysregulation also occurs during neurodegeneration and inflammation. Insights into this area may lead to advances in our ability to treat a range of human diseases. We are excited that our work has gotten recent press coverage on this topic: https://stanmed.stanford.edu/2019winter/cell-death-insights-inspire-treatments.html
Courses Taught
CHEM 0103
General Chemistry I
Course Description
General Chemistry I
Major topics will include atomic theory and atomic structure; chemical bonding; stoichiometry; introduction to chemical thermodynamics. States of matter; solutions and nuclear chemistry. Laboratory work deals with testing of theories by various quantitative methods. Students with strong secondary school preparation are encouraged to consult the department chair for permission to elect CHEM 0104 or CHEM 0107 in place of this course. CHEM 0103 is also an appropriate course for a student with little or no prior preparation in chemistry who would like to learn about basic chemical principles while fulfilling the SCI or DED distribution requirement. 3 hrs. lect., 3 hrs. lab, 1 hr. disc.
Terms Taught
Requirements
CHEM 0104
Upcoming
General Chemistry II
Course Description
General Chemistry II
Major topics include chemical kinetics, chemical equilibrium, acid-base equilibria, chemical thermodynamics, electrochemistry, descriptive inorganic chemistry, and coordination chemistry. Lab work includes inorganic synthesis, qualitative analysis, and quantitative analysis in kinetics, acid-base and redox chemistry. (CHEM 0103 or equivalent) 3 hrs. lect., 3 hrs. lab, 1 hr. disc.
Terms Taught
Requirements
CHEM 0313
Upcoming
Biochemistry Laboratory
Course Description
Biochemistry Laboratory
Experimental biochemistry emphasizing the isolation, purification and characterization of enzymes and the cloning of genes and expression of recombinant protein. Traditional biochemical techniques such as UV-VIS spectroscopy, gel filtration, ion exchange and affinity chromatography, electrophoresis, and immunoblotting will be used in the investigation of several enzymes. Specific experiments will emphasize enzyme purification, enzyme kinetics, and enzyme characterization by biochemical and immunochemical methods. Major techniques in molecular biology will be introduced through an extended experiment that will include DNA purification, polymerase chain reaction, bacterial transformation, DNA sequencing, and the expression, purification, and characterization of the recombinant protein. Class discussions emphasize the underlying principles of the biochemical and molecular techniques employed in the course, and how these experimental tools are improved for particular applications. Laboratory reports stress experimental design, data presentation, and interpretation of results. (CHEM 0322) 2 hr. lect., 6 hrs. lab.
Terms Taught
Requirements
CHEM 0322
Biochemistry of Macromolecules
Course Description
Biochemistry of Macromolecules
This course is an introduction to biochemistry that focuses on the chemical and physical properties of amino acids, proteins, lipids, carbohydrates, and nucleic acids. Specific topics include the structure and function of proteins, enzyme mechanisms and kinetics, how carbohydrates and lipids contribute to vital cellular and organismal functions, and informational biochemistry (DNA, RNA, and specific enzymes and processes leading to the production of regulatory RNA and proteins). Specific topics from the primary literature will be explored to illustrate how particular techniques and experimental approaches are used to gain a new understanding of biochemistry and molecular biology. (CHEM 0203 or CHEM 0242) 3 hrs. lect., 1 hr. disc.
Terms Taught
CHEM 0425
Biochemistry Of Metabolism
Course Description
Biochemistry of Metabolism
A living organism requires thousands of coordinated individual chemical reactions for life. In this course we will survey the major integrated metabolic pathways of living cells and whole organisms, with particular attention to enzyme mechanisms, as well as the regulation, and integration of metabolism from the molecular to the whole organism level. The synthesis and degradation of carbohydrates, amino acids, lipids, and nucleotides are investigated, along with the mechanisms of energy flow and cell-to-cell communication. While common metabolic processes are emphasized, unique aspects of metabolism that permit cells to function in unusual niches will also be considered. Mechanistic and regulatory aspects of metabolic processes will be reinforced through an investigation of inborn errors and organic defects that lead to disease. (CHEM 0322) 3 hrs. lect., 1 hr. disc.
Terms Taught
CHEM 0500
Current
Upcoming
Independent Study
Course Description
Independent Study Project
Individual study for qualified students. (Approval required)
Terms Taught
CHEM 0700
Current
Upcoming
Senior Research
Course Description
Senior Research
In this course students complete individual projects involving laboratory research on a topic chosen by the student and a faculty advisor. Prior to registering for CHEM 0700, a student must have discussed and agreed upon a project topic with a faculty member in the Chemistry and Biochemistry Department. Attendance at all Chemistry and Biochemistry Department seminars is expected. (Approval required; open only to seniors)
Terms Taught
CHEM 0701
Current
Upcoming
Senior Thesis
Course Description
Senior Thesis
Students who have initiated research projects in CHEM 0400 and who plan to complete a senior thesis should register for CHEM 0701. Students are required to write a thesis, give a public presentation, and defend their thesis before a committee of at least three faculty members. The final grade will be determined by the department. Attendance at all Chemistry and Biochemistry Department seminars is expected. (CHEM 0400; approval required)
Terms Taught
MBBC 0700
Upcoming
Senior Independent Research
Course Description
Senior Independent Research
Seniors conducting independent research in Molecular Biology and Biochemistry under the guidance of a faculty mentor should register for MBBC 0700 unless they are completing a thesis project (in which case they should register for MBBC 0701). Additional requirements include attendance at all MBBC-sponsored seminars and seminars sponsored by the faculty mentor’s department, and participation in any scheduled meetings and disciplinary sub-groups and lab groups. (Approval required).
Terms Taught
MBBC 0701
Upcoming
Senior Thesis
Course Description
Senior Thesis
This course is for seniors completing independent thesis research in Molecular Biology and Biochemistry that was initiated in BIOL 0500, CHEM 0400, MBBC 0500, or MBBC 0700. Students will attend weekly meetings with their designated research group and engage in one-on-one meetings with their research mentor to foster understanding in their specialized research area. Students will also practice the stylistic and technical aspects of scientific writing needed to write their thesis. (BIOL 0500, CHEM 0400, MBBC 0500, MBBC 0700) (Approval required).
Terms Taught
Academic Degrees
Postdoctoral Fellowship, Microbiology and Immunology, Stanford University School of Medicine
Ph.D., Biochemistry and Molecular Biology, University of California, San Francisco (2013)
B.A., Biochemistry, Middlebury College (2006)
Publications
McNamara DE, Dovey CM, Hale AT, Quarato G, Grace CR, Guibao CD, Diep J†, Nourse A, Cai CR, Wu H, Kalathur RC, Green DR, York JD, Carette JE, and Moldoveanu T. Direct Activation of Human MLKL by a Select Repertoire of Inositol Phosphate Metabolites. Cell Chem Biol. 26, 863-877 e867. (2019) †Graduate student mentee
Study featured in journal cover artwork: https://www.cell.com/cell-chemical-biology/issue?pii=S2451-9456(18)X0007-5#\
Cao JY, Poddar A, Magtanong L, Lumb JH, Mileur TR, Reid MA, Dovey CM, Wang J, Locasale JW, Stone E, Cole SPC, Carette JE, and Dixon SJ. A Genome-wide Haploid Genetic Screen Identifies Regulators of Glutathione Abundance and Ferroptosis Sensitivity. Cell Rep. 26, 1544-1556 e1548. (2019)
Dovey CM, Diep J†, Clarke BP, Hale AT, McNamara DE, Guo H, Brown NW, Cao JY, Grace CR, Gough PJ, Bertin J, Dixon SJ, Fiedler D, Mocarski ES, Kaiser WJ, Moldoveanu T, York JD, Carette JE. MLKL Requires the Inositol Phosphate Code to Execute Necroptosis. Mol Cell. 70(5):936-948. (2018) †Graduate student mentee
Study featured in: Armitage H. “How cells self-destruct: Discoveries about the ways cells die are inspiring new disease treatments.” Stanford Medicine Magazine (Winter 2019) https://stanmed.stanford.edu/2019winter/cell-death-insights-inspire-treatments.html
Guo H, Gilley RP, Fisher A, Lane R, Landsteiner VJ, Ragan KB, Dovey CM, Carette JE, Upton JW, Mocarski ES, Kaiser WJ. Species-independent contribution of ZBP1/DAI/DLM1-triggered necroptosis in host defense against HSV1. Cell Death Dis. 9(8):816. (2018)
Wan DC, Morgan SL, Spencley AL, Mariano N, Chang EY, Shankar G, Luo Y, Li TH, Huh D, Huynh SK, Garcia JM, Dovey CM, Lumb J, Liu L, Brown KV, Bermudez A, Luong R, Zeng H, Mascetti VL, Pitteri SJ, Wang J, Tu H, Quarta M, Sebastiano V, Nusse R, Rando TA, Carette JE, Bazan JF, and Wang KC. Honey bee Royalactin unlocks conserved pluripotency pathway in mammals. Nat Commun. 9, 5078. (2018)
Mandal P, Berger SB, Pillay S, Moriwaki K, Huang C, Guo H, Lich JD, Finger J, Kasparcova V, Votta B, Ouellette M, King BW, Wisnoski D, Lakdawala AS, DeMartino MP, Casillas LN, Haile PA, Sehon CA, Marquis RW, Upton J, Daley-Bauer LP, Roback L, Ramia N, Dovey CM, Carette JE, Chan FK, Bertin J, Gough PJ, Mocarski ES, Kaiser WJ. RIP3 Induces Apoptosis Independent of Pronecrotic Kinase Activity. Mol Cell. 56(4):481-495. (2014)
Rosenberg OS*, Dovey C*, Tempesta M, Robbins RA, Finer-Moore JS, Stroud RM, Cox JS. EspR, a key regulator of Mycobacterium tuberculosis virulence, adopts a unique dimeric structure among helix-turn-helix proteins. PNAS. 108(33):13450-5. (2011) *Co-first authors
Raghavan S, Manzanillo P, Chan K, Dovey C, Cox JS. Secreted transcription factor controls Mycobacterium tuberculosis virulence. Nature. 454(7205):717-21. (2008)