Molecular Physiology & Biophysics · UVM
Molecular motors are tiny protein machines that turn chemical energy into movement, walking along tracks inside the cell to carry cargo and to push and pull on chromosomes. We study kinesins, a family of motors that move cargo, build the mitotic spindle, and segregate chromosomes. We ask how each kinesin is switched on, switched off, and adjusted for the job a particular cell needs, and why breaking that control causes cancer, bone disease, neurodevelopmental disorders, and infertility.
Research
The human genome encodes 45 kinesins. They share a conserved motor domain but behave very differently, and when their regulation fails the damage is often confined to one tissue. We work across four disease contexts, connected by a shared set of mechanistic questions.
How are motors turned on and off at the right time and place? We map post-translational modification "switches" in the motor domain (e.g. KIF18A S357 and S284, KIF11 Y211, KIF22 T158) that tune velocity, force, microtubule binding, and auto-inhibition.
Why does a mutation in a motor found in every cell damage only one tissue? We compare chondrocytes, neurons, germ cells, and tumor cells to find the mechanical and regulatory features that make a cell type vulnerable.
How do motors and other microtubule-associated proteins work together to build a spindle?
Tumor cells with chromosome instability need KIF18A to divide; normal cells don't. We study why, and what makes some tumors sensitive and others resistant to KIF18A inhibitors now in clinical trials. More below.
Patient mutations in the chromokinesin KIF22 cause SEMDJL2, a skeletal growth disorder. Mutant KIF22 stays active in anaphase and blocks spindle elongation. We test how chondrocyte spindle mechanics and the confined growth plate make bone uniquely sensitive.
Loss of kinesin-binding protein (KIFBP) causes Goldberg-Shprintzen syndrome, a neurodevelopmental disorder. KIFBP knockout cells fail to extend neurites, and we are defining how KIFBP's control of kinesins supports neuronal development.
Exome sequencing has turned up variants in kinesins linked to infertility. We are testing how these variants affect motor function and chromosome segregation.
Featured · Cancer
Many aggressive tumors, including most high-grade ovarian and triple-negative breast cancers, constantly gain and lose chromosomes. This chromosome instability (CIN) drives tumor evolution, but it also leaves cancer cells dependent on mitotic machinery that normal cells can do without. KIF18A is one of those dependencies.
Depleting KIF18A causes severe spindle defects and stops proliferation in CIN tumor cells, while normal diploid cells divide with minor defects.
Marquis et al., Nat Commun 2021 · Cohen-Sharir et al., Nature 2021
KIF18A helps cells hold on to the microtubule attachments that connect chromosomes to the spindle. In sensitive tumor cells, losing KIF18A leaves some chromosomes stranded near the spindle poles and holds cells in mitosis. We are working out why CIN cells are especially vulnerable to this.
Fonseca et al., bioRxiv 2026
We identified the motor's α4 helix as a therapeutic target and helped define how two KIF18A inhibitors now in Phase I trials work.
Schutt et al., Front Mol Biosci 2024 · Phillips et al., Nat Commun 2025
Not every chromosomally unstable tumor responds to KIF18A inhibitors, and tumors that respond may adapt. What decides whether a cancer cell is sensitive or resistant, and can those features predict which patients will benefit and which drugs to combine? Genetic background matters: in mice, changes in ANAPC7 alter how strongly both germ cells and tumor cells depend on KIF18A.
Nesbit et al., Sci Rep 2025
People
Professor, Molecular Physiology & Biophysics. Co-leads the UVM Cancer Center's Cancer & Host Interactions Program.
Kinesin variants linked to infertility.
How KIFBP controls kinesins during neuronal development.
How KIF22 mutations cause SEMDJL2.
Sensitivity and resistance to KIF18A inhibitors.
Kinesin variants linked to infertility.
Microtubule organization and dynamics during neuronal differentiation.
Work-study lab assistant.
Sensitivity and resistance to KIF18A inhibitors.
UVM STEM Scholar. Sensitivity and resistance to KIF18A inhibitors.
Lab alumni have gone on to faculty positions, postdocs, PhD and medical programs, clinical practice, biotech, and industry.
| Name | Now | In lab |
|---|---|---|
| Graduate students | ||
| Katie Queen, PhD | Faculty, UVM Cancer Center | 2019–23 |
| Alex Thompson, PhD | Clinical Variant Scientist, GeneDx | 2017–22 |
| Leslie Sepaniac, PhD | Postdoc, University of Wisconsin | 2016–21 |
| Haein Kim, PhD | Business Development Officer, Stryde Research | 2013–18 |
| Anna Belongia, MS | Clinical Trials Coordinator, UVM | 2023–24 |
| Postdoctoral fellows | ||
| Katherine Schutt, PhD | Cell Biologist, Topos Bio | 2020–22 |
| Heidi Malaby, PhD | Team Lead, Complex Proposals and Strategic Positioning, UVM | 2014–19 |
| Clinical research fellows | ||
| Navin Maredia Ebrahimi, MD | Ob/Gyn, Chicago | 2024–26 |
| Carleigh Nesbit, MD | Physician, Boston IVF | 2022–24 |
| Jessica Ryniec, MD | Physician, CCRM Boston Fertility | 2018–20 |
| Staff | ||
| Kira Fisher | Senior Research Technician, UVM | 2022–26 |
| Cindy Fonseca, MS | Business owner | Staff |
A phosphorylation switch governs KIF11's mechanical output during mitosis
Šemić A, Reddy BJN, Muretta JM, Vandal SE, Thompson AF, Fonseca CL, Rosenfeld SS, Gross SP, Stumpff J
PNAS 123(33): e2602415123
Novel KIF22 variants disrupt mitosis in human chondrocytes and expand SEMDJL2 mechanisms
Šemić A, Chan KYY, Bernardi P, Silveira KC, Silveira C, Cavalcanti DP, Kannu P, Stumpff J
Mol Biol Cell 37(9): ar84
A systems-level proteomic analysis identifies kinesin targets of KIFBP during neuronal development
Paschall S, Blasius TL, Missman A, Rodriguez P, Cianfrocco MA, Verhey KJ, Stumpff J
bioRxivpreprint
Fonseca C, Fisher K, Wagner E, Paschall S, Kim H, Stumpff J
bioRxivpreprint
Meiotic spindle mechanics: Sensing a disturbance in the force
Šemić A, Stumpff J
Curr Biol 36(4): R140–R143 · Dispatch
Targeting chromosomally unstable tumors with a selective KIF18A inhibitorCIN
Phillips AF, Zhang R, … Queen KA, Racela AR, Stumpff J, … Eng CH
Nat Commun 16: 307
Anapc5 and Anapc7 as genetic modifiers of KIF18A function in fertility and mitotic progression
Nesbit C, Martin W, Czechanski A, Byers C, Raghupathy N, Ferraj A, Stumpff J, Reinholdt L
Sci Rep 15: 23046
Day CA, Grigore F, … Sepaniac L, Stumpff J, … Hinchcliffe EH
Curr Biol 35(2): 354–362
Schutt KL, Queen KA, Fisher K, Budington O, Mao W, Liu W, Gu X, Xiao Y, Aswad F, Joseph J, Stumpff J
Front Mol Biosci 11: 1328077
Modification of the neck-linker of KIF18A alters microtubule subpopulation preference
Queen KA, Cario A, Berger CL, Stumpff J
Mol Biol Cell 35(1): ar3
Pathogenic mutations in the chromokinesin KIF22 disrupt anaphase chromosome segregation
Thompson AF, Blackburn PR, Arons NS, Stevens SN, Babovic-Vuksanovic D, Lian JB, Klee EW, Stumpff J
eLife 11: e78653
Gallery
Cell art and time-lapse movies from the lab, from single motors to differentiating cells.
Images made by lab members, many created as journal cover submissions. Select an image to view it full size.
Join us
Trainees here own their projects, from the first question to the first-author paper. Each project connects a basic question about how motors work to a disease that affects real patients.
Apply through the Cellular, Molecular & Biomedical Sciences program, then reach out about a rotation.
Email Jason to talk about rotation projects in any of the four research areas.
Send a CV, a short statement of interests, and names of three references.
We host undergraduates for multi-year research and honors thesis projects. Email with your schedule and interests.
Individual training plans tied to the career you want. Alumni work in academia, medicine, biotech, and science communication.
Projects are designed together, with students leading the thinking, experimental decisions, and direction.
Trainees have won fellowships from NIH (F31), NSF (GRFP), the Department of Defense, the Vermont Space Grant Consortium, and the U.S. Department of Education.
Trainees frequently present at international meetings such as ASCB and Gordon Research Conferences.
Jason received the 2024 Research Mentor Award from the UVM Larner College of Medicine.
News
Health Science Research Facility, Room 105
149 Beaumont Avenue
Burlington, VT 05405