David A. Harris, MD, PhD
Chair of Biochemistry
Boston University Chobanian & Avedisian School of Medicine
Biochemistry & Cell Biology

MD, Columbia University
PhD, Columbia University
BS, Yale University



Expertise in prion diseases and Alzheimer’s disease.

My laboratory investigates the molecular and cellular mechanisms underlying two classes of human neurodegenerative disorders: prion diseases and Alzheimer’s disease. Alzheimer’s disease afflicts 5 million people in the U.S., a number that will increase dramatically as the population ages. Prion diseases are much rarer, but are of great public health concern because of the global emergence of bovine spongiform encephalopathy (“mad cow disease”), and its likely transmission to human beings. Moreover, prions exemplify a novel mechanism of biological information transfer based on self-propagating changes in protein conformation, rather than on inheritance of nucleic acid sequence. Prion and Alzheimer’s diseases are part of a larger group of neurodegenerative disorders, including Parkinson’s, Huntington’s and several other diseases, which are due to protein misfolding and aggregation. A prion-like process may be responsible for the spread of brain pathology in several of these disorders, and there is evidence that the prion protein itself may serve as a cell-surface receptor mediating the neurotoxic effects of multiple kinds of misfolded protein. Thus, our work on prion and Alzheimer’s diseases will likely provide important insights into a number of other chronic, neurodegenerative disorders.

Our work has several broad objectives. First, we wish to understand how the cellular form of the prion protein (PrPC) is converted into the infectious form (PrPSc). To address this question, we have investigated the cellular localization and trafficking of both PrPC and PrPSc, the nature of their association with cell membranes, as well as the molecular features of the conversion process itself. Second, we want to understand how prions and other misfolded protein aggregates cause neurodegeneration, neuronal death and synaptic dysfunction. In this regard, we seek to identify what molecular forms of PrP and the Alzheimer’s Aß peptide represent the proximate neurotoxic species, and what receptors and cellular pathways they activate that lead to pathology. Third, we aim to use our knowledge of the cell biology of prion and Alzheimer’s diseases to develop drug molecules for treatment of these disorders.

We utilize a range of experimental systems and models, including transgenic mice, cultured mammalian cells, yeast (S. cerevisiae), and in vitro systems. We employ a wide variety of techniques, including protein chemistry, light and electron microscopy, mouse transgenetics, high-throughput screening, neuropathological analysis, biophysical techniques (surface plasmon resonance, NMR, X-ray crystallography), electrophysiology (patch-clamping), medicinal chemistry, and drug discovery approaches.

Edgar Minas Housepian, MD Professor
Boston University Chobanian & Avedisian School of Medicine
Biochemistry & Cell Biology


Member
Boston University
Evans Center for Interdisciplinary Biomedical Research


Member
Boston University
Genome Science Institute


Graduate Faculty (Primary Mentor of Grad Students)
Boston University Chobanian & Avedisian School of Medicine, Graduate Medical Sciences




Mechanisms of Neurodegeneration in Hereditary Prion Diseases
06/01/2025 - 05/31/2030 (PI)
NIH/National Institute of Neurological Disorders & Stroke
1R01NS143202-01

The role of astrocytes in prion strain susceptibility
09/01/2025 - 08/31/2028 (Key Person / Mentor)
NIH/National Institute of Neurological Disorders & Stroke
1F31NS139614-01A1

Mechanisms of Prion Protein Toxicity
07/01/2021 - 06/30/2026 (PI)
NIH/National Institute of Neurological Disorders & Stroke
5R01NS065244-15

Discovering How Cu(II)/Zn(II) Uptake by the Prion Protein Controls Structure, Function and Neurotoxicity
07/01/2019 - 04/30/2026 (Subcontract PI)
The University of California, Santa Cruz NIH NIGMS
5R35GM131781-07

Characterization of synaptic abnormalities in iPSC-derived neurons from E200K carriers
03/01/2025 - 02/28/2026 (Key Person / Mentor)
PI: Jose Andres Alepuz Guillen, PhD
Creutzfeldt-Jakob Diseases Foundation, Inc.


Micro-Mapping to Identify Receptors for Toxic Protein Oligomers in Neurodegenerative Diseases
02/10/2022 - 06/30/2024 (PI)
Merck, Sharp & Dohme LLC


Identification of Receptors for TDP-43 That Mediate Cellular Uptake and Neurotoxicity
02/15/2021 - 08/14/2023 (Key Person / Mentor)
PI: Robert C. Mercer, PhD
Department of Defense/Army Medical Research Acquisition Activity


Signaling Pathways Underlying Prion Neurotoxicity
05/01/2019 - 04/30/2022 (Key Person / Mentor)
PI: Nhat Le, PhD
Warren Alpert Foundation


Genomic and Proteomic Analysis of Prion Synaptotoxicity
09/15/2018 - 08/31/2021 (PI)
NIH/National Institute of Neurological Disorders & Stroke
5R21NS107755-02

Mechanisms of Prion Protein Toxicity
03/01/2016 - 06/30/2021 (PI)
NIH/National Institute of Neurological Disorders & Stroke
5R01NS065244-10

Showing 10 of 21 results. Show All Results


Title


Yr Title Project-Sub Proj Pubs
2025 Mechanisms of Neurodegeneration in Hereditary Prion Diseases 1R01NS143202-01
2025 Mechanisms of Prion Protein Toxicity 5R01NS065244-15
2024 Mechanisms of Prion Protein Toxicity 5R01NS065244-14
2023 Mechanisms of Prion Protein Toxicity 5R01NS065244-13
2022 Mechanisms of Prion Protein Toxicity 5R01NS065244-12
2021 Mechanisms of Prion Protein Toxicity 2R01NS065244-11A1 29
2020 Mechanisms of Prion Protein Toxicity 5R01NS065244-10 29
2019 Modeling prion diseases using human iPSC-derived neurons 1R21NS111499-01
2019 Genomic and Proteomic Analysis of Prion Synaptotoxicity 5R21NS107755-02 2
2019 Mechanisms of Prion Protein Toxicity 5R01NS065244-09 29
Showing 10 of 88 results. Show All Results

Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.

iCite Website       Copy PMIDs To Clipboard

  1. Mercer RCC, Le NTT, Mirza-Romero NA, Flaherty E, DeFranco JP, Lavigna G, Orbe IC, Gatdula JRP, Fraser DG, Sundaravadivelu A, Vultaggio JS, Beeler AB, Chiesa R, Telling GC, Harris DA. Lysosomal Enhancement Prevents Infection with PrPSc, a-Synuclein & Tau Prions. bioRxiv. 2025 Aug 05.View Related Profiles. PMID: 40667233; PMCID: PMC12262522; DOI: 10.1101/2025.06.24.661349;
     
  2. Babygirija R, Han JH, Sonsalla MM, Matoska R, Calubag MF, Green CL, Tobon A, Yeh CY, Vertein D, Schlorf S, Illiano J, Liu Y, Grunow I, Rigby MJ, Puglielli L, Harris DA, Denu JM, Lamming DW. Fasting is required for many of the benefits of calorie restriction in the 3xTg mouse model of Alzheimer's disease. Nat Commun. 2025 Aug 04; 16(1):7147. PMID: 40759886; PMCID: PMC12322025; DOI: 10.1038/s41467-025-62416-3;
     
  3. Hordijk I, Poorter L, Liang J, Reich PB, de-Miguel S, Nabuurs GJ, Gamarra JGP, Chen HYH, Zhou M, Wiser SK, Pretzsch H, Paquette A, Picard N, Hérault B, Bastin JF, Alberti G, Abegg M, Adou Yao YC, Almeyda Zambrano AM, Alvarado BV, Alvarez-Davila E, Alvarez-Loayza P, Alves LF, Amaral I, Ammer C, Antón-Fernández C, Araujo-Murakami A, Arroyo L, Avitabile V, Aymard C GA, Baker T, Banki O, Barroso J, Bastian ML, Birigazzi L, Birnbaum P, Bitariho R, Boeckx P, Bongers F, Bouriaud O, Brancalion PHS, Brandl S, Brearley FQ, Brienen R, Broadbent EN, Bruelheide H, Cazzolla Gatti R, Cesar RG, Cesljar G, Chazdon RL, Chisholm C, Cienciala E, Clark CJ, Clark DB, Colletta G, Coomes D, Cornejo Valverde F, Corral-Rivas JJ, Crim P, Cumming J, Dayanandan S, de Gasper AL, Decuyper M, Derroire G, DeVries B, Djordjevic I, Dourdain A, Dolezal J, Engone Obiang NL, Enquist B, Eyre T, Fandohan AB, Fayle TM, Ferreira LV, Feldpausch TR, Finér L, Fischer M, Fletcher C, Frizzera L, Gianelle D, Glick HB, Harris D, Hector A, Hemp A, Herbohn J, Hillers A, Honorio Coronado EN, Hui C, Cho H, Ibanez T, Jung I, Imai N, Jagodzinski AM, Jaroszewicz B, Johannsen V, Joly CA, Jucker T, Karminov V, Kartawinata K, Kearsley E, Kenfack D, Kennard D, Kepfer-Rojas S, Keppel G, Khan ML, Killeen T, Kim HS, Kitayama K, Köhl M, Korjus H, Kraxner F, Laarmann D, Lang M, Lewis S, Lu H, Lukina N, Maitner B, Malhi Y, Marcon E, Marimon BS, Marimon-Junior BH, Marshall AR, Martin E, Martynenko O, Meave JA, Melo-Cruz O, Mendoza C, Merow C, Miscicki S, Monteagudo Mendoza A, Moreno V, Mukul SA, Mundhenk P, Nava-Miranda MG, Neill D, Neldner V, Nevenic R, Ngugi M, Niklaus PA, Oleksyn J, Ontikov P, Ortiz-Malavasi E, Pan Y, Parada-Gutierrez A, Parfenova E, Park M, Parren M, Parthasarathy N, Peri PL, Pfautsch S, Phillips OL, Piedade MT, Piotto D, Pitman NCA, Pollastrini M, Polo I, Poulsen AD, Poulsen JR, Arevalo FR, Restrepo-Correa Z, Rodeghiero M, Rolim S, Roopsind A, Rovero F, Rutishauser E, Saikia P, Salas-Eljatib C, Schall P, Schepaschenko D, Scherer-Lorenzen M, Schmid B, Schöngart J, Searle EB, Seben V, Selvi F, Serra-Diaz JM, Sheil D, Shvidenko A, Silva-Espejo J, Silveira M, Singh J, Sist P, Slik F, Sonké B, Souza AF, Ter Steege H, Sterenczak K, Svenning JC, Svoboda M, Swanepoel B, Targhetta N, Tchebakova N, Thomas R, Tikhonova E, Umunay P, Usoltsev V, Valencia R, Valladares F, van der Plas F, Van Do T, Van Nuland ME, Vasquez Martinez R, Verbeeck H, Viana H, Vibrans AC, Vieira S, von Gadow K, Wang HF, Watson J, Werner GDA, Wittmann F, Wortel V, Zagt R, Zawila-Niedzwiecki T, Zhang C, Zhao X, Zhu ZX, Zo-Bi IC, Maynard DS, Crowther TW. Effect of climate on traits of dominant and rare tree species in the world's forests. Nat Commun. 2025 May 22; 16(1):4773. PMID: 40404639; PMCID: PMC12098762; DOI: 10.1038/s41467-025-59754-7;
     
  4. Di Giovannantonio M, Hartley F, Elshenawy B, Barberis A, Hudson D, Shafique HS, Allott VES, Harris DA, Lord SR, Haider S, Harris AL, Buffa FM, Harris BHL. Defining hypoxia in cancer: A landmark evaluation of hypoxia gene expression signatures. Cell Genom. 2025 Feb 12; 5(2):100764. PMID: 39892389; PMCID: PMC11872601; DOI: 10.1016/j.xgen.2025.100764;
     
  5. Ali R, Li H, Zhang H, Pan W, Reeder SB, Harris D, Masch W, Aslam A, Shanbhogue K, Bernieh A, Ranganathan S, Parikh N, Dillman JR, He L. Multi-site, multi-vendor development and validation of a deep learning model for liver stiffness prediction using abdominal biparametric MRI. Eur Radiol. 2025 Jul; 35(7):4362-4373. PMID: 39779515
     
  6. Zhang H, Li H, Ali R, Jia W, Pan W, Reeder SB, Harris D, Masch W, Aslam A, Shanbhogue K, Parikh NA, Dillman JR, He L. Development and Validation of a Modality-Invariant 3D Swin U-Net Transformer for Liver and Spleen Segmentation on Multi-Site Clinical Bi-parametric MR Images. J Imaging Inform Med. 2024 Dec 20. PMID: 39707114
     
  7. Shaefer HL, Hanna M, Harris D, Richardson D, Laker M. Protecting the health of children with universal child cash benefits. Lancet. 2024 Dec 07; 404(10469):2380-2391. PMID: 39645379
     
  8. Gojanovich AD, Le NTT, Mercer RCC, Park S, Wu B, Anane A, Vultaggio JS, Mostoslavsky G, Harris DA. Abnormal synaptic architecture in iPSC-derived neurons from a multi-generational family with genetic Creutzfeldt-Jakob disease. Stem Cell Reports. 2024 Oct 08; 19(10):1474-1488.View Related Profiles. PMID: 39332406; PMCID: PMC11561462; DOI: 10.1016/j.stemcr.2024.08.010;
     
  9. Chen Y, Chaudhari SN, Harris DA, Roberts CF, Moscalu A, Mathur V, Zhao L, Tavakkoli A, Devlin AS, Sheu EG. A small intestinal bile acid modulates the gut microbiome to improve host metabolic phenotypes following bariatric surgery. Cell Host Microbe. 2024 Aug 14; 32(8):1315-1330.e5. PMID: 39043190; PMCID: PMC11332993; DOI: 10.1016/j.chom.2024.06.014;
     
  10. Mercer RCC, Le NTT, Fraser DG, Houser MCQ, Beeler AB, Harris DA. Sigma Receptor Ligands Are Potent Antiprion Compounds that Act Independently of Sigma Receptor Binding. ACS Chem Neurosci. 2024 Jun 05; 15(11):2265-2282.View Related Profiles. PMID: 38743607; PMCID: PMC12172621; DOI: 10.1021/acschemneuro.4c00095;
     
Showing 10 of 165 results. Show More

This graph shows the total number of publications by year, by first, middle/unknown, or last author.

Bar chart showing 165 publications over 42 distinct years, with a maximum of 9 publications in 2001 and 2007

YearPublications
19801
19811
19821
19831
19841
19881
19892
19901
19913
19935
19941
19954
19964
19975
19986
19997
20008
20019
20023
20037
20045
20056
20061
20079
20086
20096
20104
20115
20124
20134
20143
20151
20166
20174
20182
20195
20203
20214
20222
20233
20246
20255


Treatments that maintain the health of synapses may help prevent, mitigate the symptoms of prion disease

Medical Xpress 9/27/2024

Foiling Deadly Prions

Science Magazine 3/21/2024

Five Faculty Receive Edward Avedisian Professorships

BU Today 3/21/2024

Prion Disease Harms Neurons via Stress Pathway

Genetic Engineering & Biotechnology News 9/24/2018

1991-1994 Klingenstein Fellowship Award in the Neurosciences
1986-1991 National Institutes of Health: Clinical Investigator Development Award
1983 Columbia College of Physicians & Surgeons: Titus Munson Coan Prize
1983-1985 National Institutes of Health: Individual National Research Service Award
1983 Columbia College of Physicians & Surgeons: Frederick P. Gay Memorial Award
1981 Columbia College of Physicians & Surgeons: Alfred Steiner Research Award
In addition to these self-described keywords below, a list of MeSH based concepts is available here.

Prion Diseases
Alzheimer's Disease
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