13390-Lahiri, Debomoy

Debomoy K. Lahiri, PhD

Distinguished Professor

NB 200C, Neuroscience Research Bldg.

Indianapolis, IN
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My work balances teaching and research on the neurobiology and genetics of aging and Alzheimer’s disease (AD). I particularly enjoy working with and teaching medical students, graduate students, residents and fellows. I also give presentations on my research at national and international conferences. My main research interest is to understand how degeneration of brain cells under laboratory conditions can be more closely made to resemble the “natural” neurodegeneration of AD. This can be used to test drugs to prevent or even reverse AD-related degeneration. In particular, I am most interested in how stress from the environment leads to brain nerve cell damage in AD.

I have published over 300 peer-reviewed articles, authored four books and received several patents, much of that in collaboration with others. I have received external grants from National Institute on Aging/NIH (R01, R03, R21, R41 and P30), the Alzheimer’s Association, and drug companies, e.g., Baxter Healthcare, Forest Research, Janssen, Novartis, and QR Pharma. I mentor Masters, PhD, MD/PhD students, and postdoctoral fellows. In my commitment to disseminate knowledge, I also serve as the Editor-In-Chief of a respected, peer-reviewed international journal, Current Alzheimer Research, which publishes articles on basic, clinical, and translational research from diverse areas of AD. I am a Core leader and member of the Indiana Alzheimer’s Disease Center (IADC) Executive Committee. I was particularly humbled to receive the Zenith Fellow Award. 

I was also named a 2022 fellow of the National Academy of Inventors – the highest professional distinction awarded to academic inventors.

Some of my most notable work includes:

  • The development of Posiphen, also known as Buntanetap, an experimental drug currently in late-stage clinical trials for Alzheimer's disease and related disorders. Research by Lahiri found that Posiphen lowered amyloid-beta peptide levels in cell culture and mice. This work is significant as the presence of amyloid-beta peptide-loaded neuritic plaques is one of the hallmarks of Alzheimer’s disease.
  • The invention of cellular and biochemical approaches to prevent the accumulation of potentially toxic amyloid beta peptide in the central nervous system. These methods involve administering a chemical compound that can penetrate the blood-brain barrier to patients at risk of developing dementia. Both Alzheimer's and Down syndrome patients would benefit from the paradigm, as Down syndrome has been linked to increased brain amyloid levels and early-onset Alzheimer's disease.
  • The invention of methods for the stimulation of synthesis of synaptophysin, an integral membrane protein localized to neurotransmitter-bearing vesicles, in the central nervous system. A method of increasing the synthesis and/or secretion of synaptophysin comprises administering an effective quantity of certain therapeutic compounds.
  • Demonstrating the use of memantine, a drug used to treat Alzheimer’s disease symptoms, to modify the deposition of proteins associated with neurodegeneration. Specifically, the invention relates to the ability of memantine to intervene in the processing of amyloid-beta precursor protein and decrease the levels of fibrillogenic amyloid beta peptides. This invention was licensed to AbbVie, a subsidiary of Forest Laboratories in New York City.
  • The discovery of a relationship between Alzheimer's disease-associated proteins, autism spectrum disorder and fragile X syndrome. Lahiri co-invented a method to monitor autism spectrum disorder and fragile X syndrome patients by measuring blood plasma levels of a molecule involved in changes to learning and memory and using these levels to adjust the dose of a therapeutic compound called acamprosate.
  • Demonstrating that acamprosate, a prescription medication for alcoholism, could reduce the activation of a cell signaling pathway associated with many of the symptoms of autism spectrum disorder. Accordingly, in addition to its utility as a diagnostic marker for autism spectrum disorder, researchers found the pathway's relative activation can be used to monitor patients treated with acamprosate.
  • The co-invention of methods to treat neurodegenerative diseases by targeting inflammatory pathways. In addition to amyloid plaques, neuroinflammation triggers Alzheimer's disease. This invention provides pharmaceutical compositions comprising rationally designed peptides that interfere with the NF-κB signaling pathway, which has been a catalyst for intense drug discovery and development, including by Indiana-based company Provaidya, LLC.
  • The invention of a novel genomic DNA extraction method from human subjects, which led to several genomics discoveries. This method is used in laboratories worldwide for human genome mapping and genotyping, and the research has been cited by peer scientists over 2,700 times – a record number of citations for a research publication from a single IU School of Medicine lab.
  • Demonstrating how a genotype called apolipoprotein E influences the effect of cholinomimetic drugs, such as tacrine, which is used to treat the symptoms of mild to moderate Alzheimer’s disease, on patients' clinical outcomes.
  • Proposing the “Latent Early-life Associated Regulation” (LEARn) pathway that unites genes and the environment. Over time, environmentally induced epigenomic changes can result in an increased risk of dementia, but individually these changes are essentially latent. The biochemical basis of LEARn leads to a novel remedial possibility that a high-risk individual’s impending dementia could be averted through environmental changes, including not only therapeutic intervention, but also healthy lifestyle choices and other environmental adjustments.
  • The discovery of a more novel target for neurodegenerative disease therapies: the unique roles of specific microRNA species in Alzheimer's disease.

Titles & Appointments

  • Distinguished Professor
  • Professor of Psychiatry
  • Professor of Medical & Molecular Genetics
  • Professor of Psychiatry
  • Education
    1989 FEL Neurobiology- Alzheimer's disease, Mount Sinai School of Medicine New York
    1980 PhD Banaras Hindu University
    1975 MS Banaras Hindu University
    1973 BS Banaras Hindu University
  • Research

    My primary focus is to understand the mechanisms of aging and longevity of the brain; origin and biogenesis of AD-associated amyloid plaque; and gene regulation related to AD and other neuropsychiatric disorders. My main goal is to better understand the causes of neurodegenerative diseases (such as AD), to determine molecular methods for their diagnoses, and to devise rational neuroprotective strategies for prevention and treatment of such age-related disorders.

    I played a key role in elucidating the molecular pathway for the amyloid-β precursor protein (APP) and its metabolites in AD at Mount Sinai School of Medicine, New York. At the Indiana University School of Medicine, I expanded my research to neurobiology of brain injury, epigenetics, and how autism spectrum disorder and fragile X syndrome may relate to AD, a particularly novel discovery. In addition, we have begun to explore parallels between the progressive damage of AD and long-term effects of traumatic brain injury (TBI). My team has led characterization of the regulatory regions (promoters) of several AD-associated genes. We were among the first to demonstrate non-cholinergic properties of the cholinesterase inhibitors widely-used in AD treatment. We first proposed the “Latent Early-life Associated Regulation” (LEARn) model that unites genes and environment. LEARn posits that early-life exposures (“hits”) may be latently “stored” in the epigenome until sufficient hits accumulate to produce late-life disorders, such as AD. LEARn proposes specific, testable mechanisms and targets as an alternative to “black-boxing” the gene-environment interaction. In response to advances in epigenetics research, we further refined LEARn as the “Transgenerational-LEARn” model (t-LEARn).

    A more novel target that has grown out of our work is elucidating the neurobiology of microRNA (miRNA). We discovered unique roles of specific miRNA species in AD. Since AD-associated gene regulation includes mRNA translation, discovery of specific miRNA operating on AD-associated mRNAs is significant. We are testing how levels of specific miRNAs could be novel markers for AD risk and co-regulation of AD and TBI-associated protein levels by miRNA species.

  • Professional Organizations
    American Association for the Advancement of Science
    American Society for Biochemistry and Molecular Biology
    American Society for Neurochemistry
    Indiana State Department of Health (ISDH)
    Listed in Marquis Who's Who in America (2012-present).
    Society for Neuroscience
  • Clinical Interests

    My clinical interests are translational, collaborative and limited to using well-characterized human samples (plasma, CSF and brain tissues). I have established strong ties with clinical researchers in order to apply a translational component to my research in AD, TBI, and Autism Spectrum Disorders (ASD). We have already discovered evidence that two disorders, AD and ASD, are “associated but opposite”. That is AD and the Autism may have fundamental molecular contrasts. This we observed when comparing those APP processing pathways associated with AD (amyloidogenic) with those of ASD (anabolic). Unraveling regulation of both pathways may point toward common molecular targets that can be fine-tuned according to the appropriate life stage.

  • Awards
    Org: National Academy of Inventors
    Desc: Fellow
    Scope: National
    Date: 2022-11-28
    Desc: Trustee Teaching Award
    Scope: University
    Date: 2021-05-01
    Org: Indiana University
    Desc: Distinguished Professor
    Scope: University
    Date: 2021-02-05
    Org: American Association for the Advancement of Science
    Desc: Fellow (Neuroscience)
    Scope: National
    Date: 2020-11-02

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