David A. Harris, MD, PhD

Chair of Biochemistry, Boston University Chobanian & Avedisian School of Medicine

Biography

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.

Publications

  • Published 8/4/2025

    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.

    Read at: PubMed

  • Published 5/22/2025

    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.

    Read at: PubMed

  • Published 1/31/2025

    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.

    Read at: PubMed

  • Published 1/9/2025

    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.

    Read at: PubMed

  • Published 12/20/2024

    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.

    Read at: PubMed

Other Positions

  • Edgar Minas Housepian, MD Professor, Biochemistry & Cell Biology
    Boston University Chobanian & Avedisian School of Medicine
  • Member, Evans Center for Interdisciplinary Biomedical Research
    Boston University
  • Member, Genome Science Institute
    Boston University
  • Graduate Faculty (Primary Mentor of Grad Students)
    Boston University Chobanian & Avedisian School of Medicine, Graduate Medical Sciences

Education

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