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David F Kashatus

David F Kashatus

Associate Professor, Microbiology, Immunology, and Cancer Biology

Primary Location
PO Box 800734 Health System Pinn Hall;
Room 7045
Charlottesville, VA 22908
Primary Phone Number
434.924.0090
Fax Number
434.982.1071
Email
[email protected]
Website
https://mic.med.virginia.edu/kashatus/

Bio & Overview

Introduction: Mitochondria are often pictured in biology texts as static, individual organelles, when in reality they form highly dynamic and mobile networks constantly undergoing fusion and fission. Research in the last decade has revealed that mitochondrial fusion and fission impact nearly every aspect of mitochondrial function, from cellular metabolism, to calcium homeostasis, to the control of cell survival through apoptosis and autophagy. In addition, failure to properly maintain this dynamic mitochondrial network has been shown to play a role in a number of diseases, including Parkinson's disease, Alzheimer's disease, diabetes and cancer. The goals of our research are: (1) to uncover the molecular mechanisms that directly control mitochondrial dynamics, (2) to identify and characterize signaling pathways that interact with the mitochondrial dynamics machinery and (3) to determine how these interactions impact the pathology of diseases such as cancer. Research Projects: 1. Cell cycle regulation of mitochondrial fission: Equal distribution of mitochondria to daughter cells requires that the mitochondrial network undergo fission prior to cell division. The mitotic division of mitochondria is a highly regulated process that depends on both the mitochondrial recruitment and phosphorylation of the large GTPase Drp1. Several proteins are known to play a role in this process, including the kinases Cdk1 and Aurora A, the small GTPase RalA, and the large, multifunctional protein RalBP1. Using a combination of biochemistry, cell biology and molecular genetics we are elucidating the molecular details of how these proteins collaborate to carry out this process and exploring the consequences when the process is disrupted. 2. Pathways that regulate mitochondrial dynamics: A number of important cellular processes are accompanied by changes in the mitochondrial network, but the signaling pathways that link these processes to the mitochondrial fusion and fission machinery are not well understood. Using unbiased approaches such as large-scale proteomic and RNAi screens, as well as more targeted gain- and loss-of-function analyses, we are identifying and characterizing signaling pathways that regulate mitochondrial fusion and fission. Furthermore, using a combination of biochemistry, molecular genetics and cell biology, we investigate how these pathways interact with the core mitochondrial fusion and fission machinery, the large fission GTPase Drp1, and the fusion-mediating GTPases Mfn1, Mfn2 and Opa1. 3. Mitochondrial dynamics in cancer: Mitochondrial dynamics have been shown to be important for the cellular control of apoptosis, autophagy and metabolic function, processes that are critical regulators of tumorigenesis. As such, it is essential that we understand the molecular basis of how various oncogenic signaling pathways converge upon the fusion and fission machinery and how mitochondrial dynamics contribute to oncogenic transformation and tumorigenesis. To that end, we use xenografts of human cancer cell lines and genetically engineered mouse models to determine the role that mitochondria shaping proteins play in the initiation and maintenance of human tumors.

Academic Information

Department
Microbiology, Immunology, and Cancer Biology
Academic Title
Associate Professor

Primary Education

  • AB, Ecology & Evolutionary Biology, Princeton University, 1997
  • PhD, Genetics and Molecular Biology, University of North Carolina, 2006

Other Appointments

  • Assistant Professor, Microbiology, Immunology, and Cancer Biology
  • Cell Biology

Other Affiliations

  • Cancer Center
  • MSTP
  • Assistant Professor, BIMS
  • BIMS

Research Interests

The Role of Mitochondrial Fusion and Fission in Tumorigenesis.

Research Disciplines

  • Biochemistry
  • Cancer Biology
  • Cell and Developmental Biology
  • Metabolism
  • Molecular Biology

Research Opportunities

  • Cancer Biology
  • Cell Biology
  • Cellular and Molecular Metabolism

PhD Programs

  • Biochemistry & Molecular Genetics
  • Cell Biology
  • Microbiology

Selected Publications

2026

Yang R, Zheng K, Metts M, Wang Y, Yin D, Li KP, Prazmowska AA, Kashatus DF, Kuhlman B, Yang J, De novo design of protein binders that target DELE1 to inhibit the mitochondrial stress response, eLife15:RP111905 doi: 10.7554/eLife.111905.1

Sharmin S, Kashatus JA, Adair SJ, BakallLoewgren E, Fallahi-Sichani M, Bauer TW, Kashatus DF, Reactivation of DRP1 plays a functional role in resistance to MEK inhibition in pancreatic cancer cells, Brit J Cancer, doi: 10.1038/s41416-026-03542-7

Burge RA, Le Roux O, Popow O, Spadafora V, Helke KL, Dincman TA, Adair SJ, Bialousow L, Taquey MC, Saberi S, Sharma S, Ostrowski MC, Guttridge DC, Bauer TW, Kashatus DF, Vaena S, Allen S, Han L, McFall T, Haigis KM, Hollingsworth MA, Counter CM, Der CJ and Hobbs GA, KRASG12R-mutant Pancreatic Cancer has Reduced ERK/MAPK Transcriptional Control and a Distinct Tumor Microenvironment, Cancer Res., 86(8):1868- doi: 10.1158/0008-5472.CAN-25-2630

Burge RA, Bialousow L, Linke A, Coalson HS, Adair SJ, Sundararaj K, Smith M, Bumbleburg C, Bauer TW, Kashatus DF, Hobbs GA, PTEN oxidation promotes constitutive PI3K signaling and inducible macropinocytosis in pancreatic cancer, Cancer Res., 86(8):1854- doi: 10.1158/0008-5472.CAN-24-4501

2025

Pacheco GG, Dzamba BJ, Endo W, Edwards BC, Khan M, Comlekoglu T, Shook DR, Quasey K, Kashatus DF, DeSimone DW, Integrin mechanotransduction drives mitochondrial membrane potential during collective mesendoderm migration, Cell Sci., 138(9), doi: 10.1242/jcs.263665

Prevost CT, Gansereit WB, Kashatus DF, NRF2 regulates lipid droplet dynamics to prevent lipotoxicity, iScience, 28, 112925, doi: 10.1016/j.isci.2025.112925

2024

Ferretti, G. D. S., Quaas, C. E., Bertolini, I., Zuccotti, A., Saatci, O., Kashatus, J. A., . . . Barnoud, T. (2024). HSP70-mediated mitochondrial dynamics and autophagy represent a novel vulnerability in pancreatic cancer. CELL DEATH AND DIFFERENTIATION, 31(7), 881-896. doi:10.1038/s41418-024-01310-9

Sweatt AJ, Griffiths CD, Groves S, Paudel BB, Wang L, Kashatus DF, and Janes KA, Proteome-wide copy-number estimation from transcriptomics, Molecular Systems Biology, 20(11):1230-1256, doi: 10.1038/s44320-024-00064-3

Francois, AK, Rohani A, Loftus M, Dochnal S, Hrit J, McFarlane S, Whitford A, Lewis A, Krakowiak P, Boutell C, Rothbart S, Kashatus DF, Cliffe AR, Single-genome analysis reveals heterogeneous association of the Herpes Simplex Virus genome with H3K27me2 and the reader PHF20L1 following infection of human fibroblasts, mBio, e03278-23, doi: 10.1128/mbio.03278-23

2023

Chauhan, S. S., Casillas, A. L., Vizzerra, A. D., Liou, H., Clements, A. N., Flores, C. E., . . . Warfel, N. A. (2023). PIM1 drives lipid droplet accumulation to promote proliferation and survival in prostate cancer. ONCOGENE, 43(6), 406-419. doi:10.1038/s41388-023-02914-0

2022

Sessions, D. T., Kim, K. -B., Kashatus, J. A., Churchill, N., Park, K. -S., Mayo, M. W., . . . Kashatus, D. F. (2022). Opa1 and Drp1 reciprocally regulate cristae morphology, ETC function, and NAD plus regeneration in KRas-mutant lung adenocarcinoma. CELL REPORTS, 41(11). doi:10.1016/j.celrep.2022.111818

Ozturk, H., Cingoz, H., Tufan, T., Yang, J., Adair, S. J., Tummala, K. S., . . . Adli, M. (2022). ISL2 is a putative tumor suppressor whose epigenetic silencing reprograms the metabolism of pancreatic cancer. DEVELOPMENTAL CELL, 57(11), 1331-+. doi:10.1016/j.devcel.2022.04.014

2021

Ramonett, A., Kwak, E. -A., Ahmed, T., Flores, P. C., Ortiz, H. R., Lee, Y. S., . . . Lee, N. Y. (2022). Regulation of mitochondrial fission by GIPC-mediated Drp1 retrograde transport. MOLECULAR BIOLOGY OF THE CELL, 33(1). doi:10.1091/mbc.E21-06-0286

Drake, J. C., Wilson, R. J., Laker, R. C., Guan, Y., Spaulding, H. R., Nichenko, A. S., . . . Yan, Z. (2021). Mitochondria-localized AMPK responds to local energetics and contributes to exercise and energetic stress-induced mitophagy. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 118(37). doi:10.1073/pnas.2025932118

Hussain, S. S., Tran, T. -M., Ware, T. B., Luse, M. A., Prevost, C. T., Ferguson, A. N., . . . Kashatus, D. F. (2021). RalA and PLD1 promote lipid droplet growth in response to nutrient withdrawal. CELL REPORTS, 36(4). doi:10.1016/j.celrep.2021.109451

Sessions, D. T., & Kashatus, D. F. (2021). Mitochondrial dynamics in cancer stem cells. CELLULAR AND MOLECULAR LIFE SCIENCES, 78(8), 3803-3816. doi:10.1007/s00018-021-03773-2

2020

Rohani, A., Kashatus, J. A., Sessions, D. T., Sharmin, S., & Kashatus, D. F. (2020). Mito Hacker: a set of tools to enable high-throughput analysis of mitochondrial network morphology. SCIENTIFIC REPORTS, 10(1). doi:10.1038/s41598-020-75899-5

Przanowska, R. K., Sobierajska, E., Su, Z., Jensen, K., Przanowski, P., Nagdas, S., . . . Dutta, A. (2020). miR-206 family is important for mitochondrial and muscle function, but not essential for myogenesis in vitro. FASEB JOURNAL, 34(6), 7687-7702. doi:10.1096/fj.201902855RR

Chauhan, S. S., Toth, R. K., Jensen, C. C., Casillas, A. L., Kashatus, D. F., & Warfel, N. A. (2020). PIM kinases alter mitochondrial dynamics and chemosensitivity in lung cancer. ONCOGENE, 39(12), 2597-2611. doi:10.1038/s41388-020-1168-9

2019

Nagdas, S., Kashatus, J. A., Nascimento, A., Hussain, S. S., Trainor, R. E., Pollock, S. R., . . . Kashatus, D. F. (2019). Drp1 Promotes KRas-Driven Metabolic Changes to Drive Pancreatic Tumor Growth. CELL REPORTS, 28(7), 1845-+. doi:10.1016/j.celrep.2019.07.031

Pollock, S., Schinlever, A., Rohani, A., Kashatus, J., & Kashatus, D. (2019). RalA and RalB relocalization to depolarized mitochondria depends on clathrin-mediated endocytosis and facilitates TBK1 activation. PLOS ONE, 14(4). doi:10.1371/journal.pone.0214764

2018

Hussain, S. S., & Kashatus, D. F. (2018). MDVs: Spare the SOD and Spoil the Bug. CELL HOST & MICROBE, 24(5), 616-618. doi:10.1016/j.chom.2018.10.013

Wilson, R. J., Drake, J. C., Cui, D., Lewellen, B. M., Fisher, C. C., Zhang, M., . . . Yan, Z. (2018). Mitochondrial protein S-nitrosation protects against ischemia reperfusion-induced denervation at neuromuscular junction in skeletal muscle. FREE RADICAL BIOLOGY AND MEDICINE, 117, 180-190. doi:10.1016/j.freeradbiomed.2018.02.006

Wallrabe, H., Svindrych, Z., Alam, S. R., Siller, K. H., Wang, T., Kashatus, D., . . . Periasamy, A. (2018). Segmented cell analyses to measure redox states of autofluorescent NAD(P)H, FAD & Trp in cancer cells by FLIM. SCIENTIFIC REPORTS, 8. doi:10.1038/s41598-017-18634-x

2017

Wilson, R. J., Drake, J. C., Cui, D., Zhang, M., Perry, H. M., Kashatus, J. A., . . . Yan, Z. (2019). Conditional MitoTimer reporter mice for assessment of mitochondrial structure, oxidative stress, and mitophagy. MITOCHONDRION, 44, 20-26. doi:10.1016/j.mito.2017.12.008

Perry, H. M., Huang, L., Wilson, R. J., Bajwa, A., Sesaki, H., Yan, Z., . . . Okusa, M. D. (2018). Dynamin-Related Protein 1 Deficiency Promotes Recovery from AKI. JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 29(1), 194-206. doi:10.1681/ASN.2017060659

Nascimento, A., Lannigan, J., & Kashatus, D. (2017). Detection and Quantification of Mitochondrial Fusion Using Imaging Flow Cytometry.. Current protocols in cytometry, 81, 9.53.1-9.53.13. doi:10.1002/cpcy.26

Kashatus, D. F. (2018). The regulation of tumor cell physiology by mitochondrial dynamics. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 500(1), 9-16. doi:10.1016/j.bbrc.2017.06.192

Nagdas, S., & Kashatus, D. F. (2017). The Interplay between Oncogenic Signaling Networks and Mitochondrial Dynamics. ANTIOXIDANTS, 6(2). doi:10.3390/antiox6020033

Rohani, A., Moore, J. H., Kashatus, J. A., Sesaki, H., Kashatus, D. F., & Swami, N. S. (2017). Label-Free Quantification of Intracellular Mitochondrial Dynamics Using Dielectrophoresis. ANALYTICAL CHEMISTRY, 89(11), 5758-5765. doi:10.1021/acs.analchem.6b04666

2016

Kashatus, D. F. (2016). Restraining the Divider: A Drp1-Phospholipid Interaction Inhibits Drp1 Activity and Shifts the Balance from Mitochondrial Fission to Fusion. MOLECULAR CELL, 63(6), 913-915. doi:10.1016/j.molcel.2016.08.033

Nascimento, A., Lannigan, J., & Kashatus, D. (2016). High-Throughput Detection and Quantification of Mitochondrial Fusion Through Imaging Flow Cytometry. CYTOMETRY PART A, 89A(8), 708-719. doi:10.1002/cyto.a.22891

2015

Xie, Q., Wu, Q., Horbinski, C. M., Flavahan, W. A., Yang, K., Zhou, W., . . . Rich, J. N. (2015). Mitochondrial control by DRP1 in brain tumor initiating cells. NATURE NEUROSCIENCE, 18(4), 501-+. doi:10.1038/nn.3960

Kashatus, J. A., Nascimento, A., Myers, L. J., Sher, A., Byrne, F. L., Hoehn, K. L., . . . Kashatus, D. F. (2015). Erk2 Phosphorylation of Drp1 Promotes Mitochondrial Fission and MAPK-Driven Tumor Growth. MOLECULAR CELL, 57(3), 537-551. doi:10.1016/j.molcel.2015.01.002

2013

Kashatus, D. F. (2014). An In Vitro System to Evaluate the Scaffold Function of the RalA Effector Protein RalBP1. RAS SIGNALING: METHODS AND PROTOCOLS, 1120, 207-216. doi:10.1007/978-1-62703-791-4_14

Kashatus, D. F. (2013). Ral GTPases in tumorigenesis: Emerging from the shadows. EXPERIMENTAL CELL RESEARCH, 319(15), 2337-2342. doi:10.1016/j.yexcr.2013.06.020

2012

Lampson, B. L., Kendall, S. D., Ancrile, B. B., Morrison, M. M., Shealy, M. J., Barrientos, K. S., . . . Counter, C. M. (2012). Targeting eNOS in Pancreatic Cancer. CANCER RESEARCH, 72(17), 4472-4482. doi:10.1158/0008-5472.CAN-12-0057

2011

Kashatus, D. F., & Counter, C. M. (2011). Breaking up is hard to do: RalA, mitochondrial fission and cancer.. Small GTPases, 2(6), 329-333. doi:10.4161/sgtp.18284

Kashatus, D. F., Lim, K. -H., Brady, D. C., Pershing, N. L. K., Cox, A. D., & Counter, C. M. (2011). RALA and RALBP1 regulate mitochondrial fission at mitosis. NATURE CELL BIOLOGY, 13(9), 1108-U138. doi:10.1038/ncb2310

2010

Zipfel, P. A., Brady, D. C., Kashatus, D. F., Ancrile, B. D., Tyler, D. S., & Counter, C. M. (2010). Ral activation promotes melanomagenesis. ONCOGENE, 29(34), 4859-4864. doi:10.1038/onc.2010.224

Vignola, M. J., Kashatus, D. F., Taylor, G. A., Counter, C. M., & Valdivia, R. H. (2010). cPLA2 Regulates the Expression of Type I Interferons and Intracellular Immunity to Chlamydia trachomatis. JOURNAL OF BIOLOGICAL CHEMISTRY, 285(28), 21625-21635. doi:10.1074/jbc.M110.103010