Bess  Frost, Ph.D.

We study the basic neurobiology underlying brain aging and neurodegeneration, with a strong emphasis on Alzheimer's disease and related tauopathies. We employ a multi-system approach to rapidly identify, test, and validate hypotheses that are relevant to human disease. Early discovery takes place in Drosophila, a model organism that is well suited for investigating issues of causality in disease processes. To determine if our studies are relevant to human disease, we complement Drosophila work with neuropathological and computational analyses of mouse and postmortem human brain. A major focus of the laboratory is on tau- and aging-induced activation of transposable elements and the effects of tau on nuclear and genomic architecture. 

Research Area/Field of Study: Neurodegeneration, brain aging

Sub-Field of Study: Epigenetics, RNA handling, transposable elements, novel therapeutics, Drosophila, computational biology

Associated Diseases: Alzheimer's disease and related tauopathies

• Professional Background

  Education

  • 2009 - PhD - Biomedical Sciences Program - University of California San Francisco
  • 2004 - BS - Biochemistry and Molecular Biology - University of Texas at Austin

  Training

  • 2015 - Postdoctoral Fellowship - Department of Pathology - Brigham and Women's Hospital/Harvard Medical School

  Highlights

  2020 O’Donnell Award in Medicine, The Academy of Medicine, Engineering & Science of Texas

  2019 Presidential Excellence Award for Junior Research Scholar, UTHSA, San Antonio, TX

  2016 American Federation for Aging Research New Investigator Award in Alzheimer’s Disease

  2015 Rising STARs Award: UT System

  Appointments

  • 9/2020 - Associate Professor - University of Texas Health San Antonio
  • 11/2015 - Assistant Professor/Research - University of Texas Health San Antonio
  • 2018 - Interim Director of Faculty Recruitment, Glenn Biggs Institute for Alzheimer’s & Neurodegenerative Disorders Biological Core - University of Texas Health San Antonio

• Instruction & Training

  • 2019 - Present, CSBL5089 Graduate Colloquium, Course Director , University of Texas Health San Antonio
  • 2017 - Present , INTD5043 Fundamentals of Neuroscience II: Systems Neuroscience, Lecturer, University of Texas Health San Antonio
  • 2017- Present , IBMS5000 Fundamentals of Biomedical Science, Lecturer, Lab demonstration, University of Texas Health San Antonio
  • 20017 - Present, Undergraduate Student Supervision, University of Texas Health San Antonio
  • 2017 - 2018, CSBL5089, Graduate Colloquium, Instructor, University of Texas Health San Antonio
  • 2016 - Present, CSBL5074 Intro to Research, University of Texas Health San Antonio
  • 2016 - Present , Membership on Supervising Committee, University of Texas Health San Antonio
  • 2016 - Present, Ph.D. Dissertations Directed, University of Texas Health San Antonio
  • 2016 - Present , Postdoctoral Supervision, University of Texas Health San Antonio
  • 2016 - Present, Rotation Student Supervision, University of Texas Health San Antonio
  • 2016 - Present, Individual Instruction, University of Texas Health San Antonio
  • 2016 - Present, High School School Student Supervision, University of Texas Health San Antonio

• Research & Grants

  Cell Biology

  Frost laboratory studies fundamental processes in cell biology that drive age-related neurodegenerative disorders. We employ a multi-system approach to rapidly identify, test, and validate hypotheses that are relevant to human disease. Early discovery takes place in Drosophila, a model organism that is well suited for investigating issues of causality in disease processes. To determine if our studies are relevant to human disease, we complement Drosophila work with comparative analyses in mouse and postmortem human brain tissue.

  Related diseases: Alzheimer's disease and associated tauopathies, physiological brain aging

  Frost Lab

  Grants

  • Regulation of ER-stress Activated UPR kinase PERK in Neurodegenerative Diseases
  • Regulation of neuronal clearance pathways via nuclear calcium signaling in Alzheimer’s disease
  • Investigating the role of transposable element dysregulation as a driver of neurotoxicity in tauopathy
  • Mechanisms of tau- and aging-induced neurological dysfunction: Focus on the nucleus

  Project #: N/A 01/01/20 - 12/31/20
  Funding Agency: MD Anderson Neurodegeneration Consortium
  Title: Transposable element activation as a therapeutic target in human Alzheimer’s disease and associated tauopathies
  Role: Principal Investigator
  Total Costs: $250,000.00
  Grant Detail: The scope of this work is to investigate elevated DNA copy number of transposable elements in human Alzheimer’s disease and related tauopathies, and to determine their contribution to neuroinflammation and/or somatic DNA mutation

  Project #: 1 R01 AG062475-01A1 09/01/19 - 05/31/24
  Funding Agency: NIA/NINDS
  Title: Regulation of neuronal clearance pathways via nuclear calcium signaling in Alzheimer’s disease
  Role: Co-Investigator, PI: Radek Dobrowolski
  Total Direct Costs to Frost: $631,360.00
  Grant Detail: The goal of the proposed project is to determine the mechanism whereby Presenilin 1 and tau regulate nuclear calcium and the extent to which deficits in nuclear calcium contribute to neurodegeneration.

  Project #: 1 RF1 NS112391-01 (R01 equivalent) 07/01/19 - 06/30/24
  Funding Agency: NIA/NINDS
  Title: Investigating the role of transposable element dysregulation as a driver of neurotoxicity in tauopathy
  Role: Principal Investigator
  Total Direct Costs: $1,250,000.00
  Grant Detail: The goal of the proposed project is to understand how transposable element activation induces neurotoxicity, to extend our studies to mouse models of tauopathy, and to determine the extent of transposable element activation and mobilization in human tauopathy.

  Project #: 1 R01 AG058778-01 03/01/19 - 11/30/23
  Funding Agency: NIH/NINDS
  Title: Regulation of ER-stress Activated UPR kinase PERK in Neurodegenerative Diseases
  Role: Co-Investigator, PI: James Lechleiter
  Total Direct Costs to Frost: $325,050
  Grant Detail: The major goal of this grant is to understand how cytosolic and luminal regulation of PERK activity contribute to neurodegeneration in tauopathies

  Project #: 1 R01 AG057896 02/15/19 - 11/30/23
  Funding Agency: NIA/NINDS
  Title: Mechanisms of tau- and aging-induced neurological dysfunction: Focus on the nucleus
  Role: Principal Investigator
  Total Direct Costs: $1,329,223.00
  Grant Detail: The goal of the proposed project is to identify repercussions of nuclear disruption in tauopathy and aging with a focus on RNA export.

  Project #: N/A 09/01/19 - 08/31/20
  Funding Agency: UTHSCSA Pepper Center
  Title: Evaluating the extent of transposable element activation in brain and fluid from patients with Alzheimer’s disease
  Role: Principal Investigator
  Total Costs: $25,000.00
  Grant Detail: This project utilizes single-nucleus retrotransposon capture sequencing from control and human Alzheimer’s disease brain tissue at mid- and late-stage disease to determine if transposable elements actively mobilize in the context of human Alzheimer’s disease.

  Project #: N/A 08/01/19 - 07/31/20
  Funding Agency: Rainwater Foundation/Tau Consortium
  Title: Development of a Drosophila model of prion-like tau propagation for future genetic modifier and drug screening
  Role: Principal Investigator
  Total Costs: $200,000.00
  Grant Detail: The goal of this project is to create in vivo reporters of tau aggregation and prion-like tau spread in neurons of the adult Drosophila brain.

  Project #: N/A 06/01/19 - 05/31/20
  Funding Agency: William and Ella Owens Medical Research Foundation
  Title: Dysregulation of Transposable Element Sequences as a Novel Disease Mechanism in Alzheimer’s Disease and Related Tauopathies
  Role: Principal Investigator
  Total Costs: $100,000.00
  Grant Detail: The goal of this project was to determine if transposable elements actively mobilize in human tauopathy.

  Project #: N/A 05/01/19 - 04/31/20
  Funding Agency: MD Anderson Neurodegeneration Consortium
  Title: Reverse transcriptase inhibitors for Alzheimer’s disease
  Role: Principal Investigator
  Total Costs: $100,000.00
  Grant Detail: The scope of this work was to investigate transposable element activation and reverse transcriptase activity in human Alzheimer’s disease and related tauopathies, and to validate candidate proteins as potential therapeutic targets.

  Project #: N/A 01/01/19 - 12/31/19
  Funding Agency: Center for Biomedical Neurosciences Pilot Grant
  Title: Testing 3TC as a novel therapeutic for transposable element activation and consequent neurodegeneration in a mouse model of tauopathy
  Role: Principal Investigator
  Total Costs: $50,000.00
  Grant Detail: The goals of this project were to determine if orally administered 3TC penetrates the mouse brain and suppresses tau-induced neurotoxicity.

  Project #: N/A 08/01/18 - 07/31/19
  Funding Agency: Rainwater Foundation/Tau Consortium
  Title: Investigating transposable element activation as a causal mediator of neuronal death in tauopathy
  Role: Principal Investigator
  Total Costs: $200,000.00
  Grant Detail: The goal of this project was to investigate transposable element activation as a driver of neuroinflammation in neurodegenerative tauopathies, and to determine if transposable element activation occurs in mouse models of tauopathy.

  Project #: N/A 04/01/17 - 03/31/18
  Funding Agency: William and Ella Owens Medical Research Foundation
  Title: Dysregulation of Transposable Element Sequences as a Novel Disease Mechanism in Alzheimer’s Disease and Related Tauopathies
  Role: Principal Investigator
  Total Costs: $100,000.00
  Grant Detail: The goal of this project was to investigate transposable elements and piwi-interacting RNAs in a Drosophila model of tauopathy, and to determine if genetic manipulation of transposable elements modifies tau-induced neurotoxicity.

  Project #: N/A 07/01/16 - 06/30/19
  Funding Agency: American Federation for Aging Research
  Title: Investigating a Toxic Role of Nucleoplasmic Reticulum Expansion in Alzheimer’s Disease and Related Tauopathies
  Role: Principal Investigator
  Total Costs: $100,000.00
  Grant Detail: The goal of this project was to determine if nuclear envelope invaginations affect mRNA export and nuclear calcium signaling in tauopathies and aging, and to determine if these processes contribute to tau neurotoxicity.

  Project #: N/A 07/01/16 - 12/31/17
  Funding Agency: Nathan Shock Pilot Grant & Briscoe Women’s Health Scholar Fund
  Title: Investigating Loss of Terminal Differentiation of Neurons in Tauopathy
  Role: Principal Investigator
  Total Costs: $50,000.00
  Grant Detail: The goal of this project was to determine if pathological tau causes neurons to lose their terminally differentiated status, and if genetically forcing neurons to remain terminally differentiated rescues tau neurotoxicity.

  Project #: N/A 06/01/16 - 05/31/17
  Funding Agency: San Antonio Life Sciences Institute: Cluster in Research Excellence
  Title: Utilizing Imaging Mass Spectrometry and Electron Microscopy to Investigate Nucleoplasmic Reticulum Expansion in Alzheimer’s Disease
  Role: multi-PI (Bess Frost, George Perry and Stephan Bach)
  Total Costs: $100,000.00
  Grant Detail: The goal of this project was to characterize the nucleoplasmic reticulum in postmortem human Alzheimer’s disease brains using imaging mass spectrometry and focused ion beam electron microscopy.

  Project #: Rising STARs Program 11/01/15 - 10/31/17
  Funding Agency: University of Texas System
  Title: N/A
  Role: Principal Investigator
  Total Costs: $250,000.00
  Grant Detail: The purpose of the Science and Technology Acquisition and Retention Program is to encourage faculty members to perform their research at UT institutions. This award was used to purchase state-of-the art laboratory equipment.

  Project #: N/A 08/01/14 - 11/30/15
  Funding Agency: HNDC & ADRC 2014 Neurodegenerative Disease Pilot Study Grants Program
  Title: Investigating Lamin Dysfunction as a Novel Mechanism of Tau Neurotoxicity
  Role: Principal Investigator
  Total Costs: $40,000.00
  Grant Detail: The goal of this project was to utilize super-resolution microscopy to visualize the interaction between lamin and heterochromatin in tauopathy.

  Project #: 1 K99/R00 NS 088429 08/01/14 - 11/30/19
  Funding Agency: NIH/NINDS
  Title: Mechanisms and Consequences of Heterochromatin Loss in Tauopathies
  Role: Principal Investigator
  Total Costs: $932,754.00
  Grant Detail: The goal of this project was to probe lamin dysfunction as the cause of heterochromatin relaxation in tauopathies, and to investigate the expression of small and long noncoding RNAs that are abnormally expressed as a consequence of heterochromatin relaxation in tauopathies.

  Project #: 1 F32 AG 039193 09/01/10 - 08/30/13
  Funding Agency: NIH/NIA
  Title: Tau-mediated chromatin regulation and neurodegeneration
  Role: Principal Investigator
  Total Costs: $145,000.00
  Grant Detail: The goal of this project was to determine if there are heterochromatic changes in tau transgenic Drosophila.

  Project #: 5T32AG000278 09/01/06 - 08/01/07
  Funding Agency: NIH/NIA
  Title: NIH Training Grant for Aging and Neurodegenerative Diseases
  Status: Complete
  Role: Trainee
  Total Costs: $28,000.00
  Grant Detail: This grant was awarded to the Hillblom Center for the Biology of Aging, directed by Dr. Cynthia Kenyon. The goal of my project was to determine if the microtubule-associated protein tau has prion-like characteristics.

  Project #: N/A 09/01/04 - 08/30/05
  Funding Agency: University of California San Francisco
  Title: Graduate Dean’s Health Science Fellowship
  Status: Complete
  Grant Detail: This fellowship is awarded to first year graduate students on the basis of scholarship, promise of outstanding achievement, and professional contribution.

  Project #: N/A 09/01/02 - 08/30/03
  Funding Agency: University of Texas Austin
  Title: University Cooperative Undergraduate Research Fellowship
  Role: PI
  Total Costs: $1,000.00
  Grant Detail: The goal of this project was to identify transcriptional changes in the mouse brain in response to chronic ethanol treatment.

• Service

  Department

  2020 - Present    Cell Systems and Anatomy Seminar Series, Organizer

  2018 - Present    Interim Director of Faculty Recruitment for the Biggs Biological Core

  2016 - Present    Cell Systems and Anatomy Susan L. Naylor Award for Excellence in Postdoctoral Studies Committee, Chair

  School

  2020 - Present  Council of Principal Investigators, member

  2016     IBMS Admissions Committee, member

   

  National Service

  Selected Grant Reviews:

  2020 NIH ZAG1 JIJ-1 (J3) Study Section (ad hoc)

  2019 - Present NIH CMND Study Section (ad hoc) 

  2019 NIH R15 Study Section (ad hoc) 

  2018 - Present AFAR Diana Jacobs Kalman Scholarship for Research in the Biology of Aging

  Reviewer for (selected):

  Nature Medicine, Nature Communications, Aging Cell, Acta Neuropathologica, Molecular Neurobiology

   

   

  Community Service

  2019 Career Day, Cambridge Elementary School, San Antonio TX

  2018 Science Demonstration, Cambridge Elementary School, San Antonio TX

  2018 President's Luncheon, Panelist, San Antonio, TX

  2017 UTHSA Night at the Movies, Panelist, San Antonio, TX

  2016 - Present Leadership San Antonio, Speaker, San Antonio, TX

  2016 Alzheimer's Association Candlelight Ceremony, San Antonio, TX

   

• Publications

  1. Frost B, Ollesch J, Wille H, Diamond MI. Conformational diversity of wild-type Tau fibrils specified by templated conformation change. J Biol Chem 2009 Feb;284(6):3546-3551.

  2. Frost B, Jacks RL, Diamond MI. Propagation of tau misfolding from the outside to the inside of a cell. J Biol Chem 2009 May;284(19):12845-12852.

  3. Frost B, Diamond MI. The expanding realm of prion phenomena in neurodegenerative disease. Prion 2009 Apr;3(2):74-77.

  4. Frost B, Diamond MI. Prion-like mechanisms in neurodegenerative diseases. Nat Rev Neurosci 2010 Mar;11(3):155- 159.

  5. Frost B, Hemberg M, Lewis J, Feany MB. Tau promotes neurodegeneration through global chromatin relaxation. Nat Neuroscience 2014 Feb;17(3):357-366.  

     **Featured as a “News and Views” in Nature Neuroscience:Soukup S, Verstreken, P. PIWIL1 protein power targets tau therapy. Nature Neuroscience. 2014 Feb;17(334-335).

  6. Merlo P, Frost B, Peng S, Yang YJ, Park PJ, Feany M. p53 prevents neurodegeneration by regulating synaptic genes. Proc Natl Acad Sci USA 2014 Dec;111(50):18055-18060.

  7. Frost B, Gotz J, Feany M. Connecting the dots between tau dysfunction and neurodegeneration. Trends in Cell Biology 2015 Jan;25(1):46-53.

  8. Frost B, Bardai FH, Feany MB. Lamin Dysfunction Mediates Neurodegeneration in Tauopathies. Current Biology 2016 Jan;26(1):129-136.

  9. Frost B. Alzheimer’s disease: An acquired neurodegenerative laminopathy. Nucleus 2016 May;7(3):275-283.  

  10. Sun W, Yan C, Frost B, Wang X, Hou C, Zeng M, Gao H, Kang Y, Liu J. Pomegranate extract decreases oxidative stress and alleviates mitochondrial impairment by activating AMPK-Nrf2 in hypothalamic paraventricular nucleus of spontaneously hypertensive rats. Scientific Reports 2016 Aug;6:342-346.

  11. Sun W, Frost B, Liu J. Oleuropein, unexpected benefits! Oncotarget 2017 Mar;14(8):17409-17409.

  12. Orr ME, Sullivan AC, Frost B. A Brief Overview of Tauopathy: Causes, Consequences, and Therapeutic Strategies.  Trends in Pharmacological Sciences 2017 Jul;38(7):637-648.

  13. Sun W, Samimi H, Gamez M, Zare H, Frost B. Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies. Nature Neuroscience 2018 Jul;21(8):1038-1048. 

     **Featured as a “Research Highlight” in Nature Reviews Neurology:  C Ridler. Does tau pathology activate jumping genes? Nature Reviews Neurology. 2018 Jul;14(559).

  14. Cornelison GL, Levy SA, Jenson T, Frost B. Tau-induced nuclear envelope invagination causes a toxic accumulation of mRNA in Drosophila. Aging Cell 2019 Feb;18(1):e12847.

  15. Ochoa Thomas E, Zuniga G, Sun W, Frost B. Awakening the dark side: Retrotransposon activation in neurodegenerative disorders. Current Opinions in Neurobiology 2020 Feb;61:65-72.

  16. Mahoney R, Ochoa Thomas E, Ramirez P, Miller HE, Beckmann A, Zuniga G, Dobrowolski R, Frost B. Pathogenic tau causes a toxic depletion of nuclear calcium mediated by BK channels. Cell Reports 2020.  32(2): 107900 PMCID: PMC 7428851.

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