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

Boston University
Evans Center for Interdisciplinary Biomedical Research

Boston University
Genome Science Institute

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

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

Discovering How Cu(II)/Zn(II) Uptake by the Prion Protein Controls Structure, Function and Neurotoxicity
07/01/2019 - 04/30/2024 (Subcontract PI)
The University of California, Santa Cruz NIH NIGMS

Micro-Mapping to Identify Receptors for Toxic Protein Oligomers in Neurodegenerative Diseases
02/10/2022 - 02/09/2024 (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

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

Modeling prion diseases using human iPSC-derived neurons
03/15/2019 - 02/28/2021 (Multi-PI)
PI: David A. Harris, MD, PhD
NIH/National Institute of Neurological Disorders & Stroke

Molecular Aspects of Copper and Zinc Binding to the Prion Protein
07/01/2015 - 06/30/2019 (Subcontract PI)
The University of California, Santa Cruz NIH NIGMS

Identification of Anti-Prion Drug Targets
04/01/2017 - 03/31/2019 (PI)
NIH/National Institute of Neurological Disorders & Stroke

Showing 10 of 18 results. Show All Results


Yr Title Project-Sub Proj Pubs
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
2018 Genomic and Proteomic Analysis of Prion Synaptotoxicity 1R21NS107755-01A1 2
2018 Identification of Anti-Prion Drug Targets 5R21NS101659-02 2
2018 Mechanisms of Prion Protein Toxicity 5R01NS065244-08 29
Showing 10 of 85 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 Analysis       Copy PMIDs To Clipboard

  1. Mercer RCC, Le NTT, Houser MCQ, Beeler AB, Harris DA. Sigma receptor ligands are potent anti-prion compounds that act independently of sigma receptor binding. bioRxiv. 2023 Nov 29.View Related Profiles. PMID: 38077011; PMCID: PMC10705434; DOI: 10.1101/2023.11.28.569035;
  2. Schilling KM, Jorwal P, Ubilla-Rodriguez NC, Assafa TE, Gatdula JRP, Vultaggio JS, Harris DA, Millhauser GL. N-glycosylation is a potent regulator of prion protein neurotoxicity. J Biol Chem. 2023 Sep; 299(9):105101.View Related Profiles. PMID: 37507020; PMCID: PMC10469999; DOI: 10.1016/j.jbc.2023.105101;
  3. Mercer RCC, Harris DA. Mechanisms of prion-induced toxicity. Cell Tissue Res. 2023 Apr; 392(1):81-96.View Related Profiles. PMID: 36070155
  4. Shafiq M, Da Vela S, Amin L, Younas N, Harris DA, Zerr I, Altmeppen HC, Svergun D, Glatzel M. The prion protein and its ligands: Insights into structure-function relationships. Biochim Biophys Acta Mol Cell Res. 2022 06; 1869(6):119240.View Related Profiles. PMID: 35192891
  5. Linsenmeier L, Mohammadi B, Shafiq M, Frontzek K, Bär J, Shrivastava AN, Damme M, Song F, Schwarz A, Da Vela S, Massignan T, Jung S, Correia A, Schmitz M, Puig B, Hornemann S, Zerr I, Tatzelt J, Biasini E, Saftig P, Schweizer M, Svergun D, Amin L, Mazzola F, Varani L, Thapa S, Gilch S, Schätzl H, Harris DA, Triller A, Mikhaylova M, Aguzzi A, Altmeppen HC, Glatzel M. Ligands binding to the prion protein induce its proteolytic release with therapeutic potential in neurodegenerative proteinopathies. Sci Adv. 2021 Nov 26; 7(48):eabj1826.View Related Profiles. PMID: 34818048; PMCID: PMC8612689; DOI: 10.1126/sciadv.abj1826;
  6. Amin L, Harris DA. Aß receptors specifically recognize molecular features displayed by fibril ends and neurotoxic oligomers. Nat Commun. 2021 06 08; 12(1):3451.View Related Profiles. PMID: 34103486; PMCID: PMC8187732; DOI: 10.1038/s41467-021-23507-z;
  7. Kim SY, Zhang F, Harris DA, Linhardt RJ. Structural Features of Heparin and Its Interactions With Cellular Prion Protein Measured by Surface Plasmon Resonance. Front Mol Biosci. 2020; 7:594497. PMID: 33324681; PMCID: PMC7726446; DOI: 10.3389/fmolb.2020.594497;
  8. Schilling KM, Tao L, Wu B, Kiblen JTM, Ubilla-Rodriguez NC, Pushie MJ, Britt RD, Roseman GP, Harris DA, Millhauser GL. Both N-Terminal and C-Terminal Histidine Residues of the Prion Protein Are Essential for Copper Coordination and Neuroprotective Self-Regulation. J Mol Biol. 2020 07 24; 432(16):4408-4425. PMID: 32473880; PMCID: PMC7387163; DOI: 10.1016/j.jmb.2020.05.020;
  9. Roseman GP, Wu B, Wadolkowski MA, Harris DA, Millhauser GL. Intrinsic toxicity of the cellular prion protein is regulated by its conserved central region. FASEB J. 2020 06; 34(6):8734-8748. PMID: 32385908; PMCID: PMC7442283; DOI: 10.1096/fj.201902749RR;
  10. Corbett GT, Wang Z, Hong W, Colom-Cadena M, Rose J, Liao M, Asfaw A, Hall TC, Ding L, DeSousa A, Frosch MP, Collinge J, Harris DA, Perkinton MS, Spires-Jones TL, Young-Pearse TL, Billinton A, Walsh DM. PrP is a central player in toxicity mediated by soluble aggregates of neurodegeneration-causing proteins. Acta Neuropathol. 2020 03; 139(3):503-526. PMID: 31853635; PMCID: PMC7035229; DOI: 10.1007/s00401-019-02114-9;
Showing 10 of 145 results. Show More

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

Bar chart showing 145 publications over 39 distinct years, with a maximum of 9 publications in 2001


Recent (within 3 months)

Foiling Deadly Prions

Science Magazine 3/21/2024

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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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