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