Madepalli Lakshmana, Ph.D. is an expert in Alzheimer’s disease (AD) with more than twenty years of experience in the field of neurodegeneration research. Dr. Lakshmana acquired basic concepts and advanced knowledge on the brain and nervous system through mandatory course work during MS, M.Phil, and Ph.D. training programs. One major focus of Dr. Lakshmana’s research is to identify molecules and pathways responsible for enhanced Aβ generation and hyperphosphorylated tau in models of AD so that those molecules can be targeted for the therapeutic benefit of AD patients. Towards this goal, Dr. Lakshmana has identified RanBP9 in a large protein complex that includes LRP, APP, BACE1, and COPS5. By generating several lines of transgenic and knockout mouse models, he could demonstrate that each one of this protein complex plays a crucial role in the amyloidogenic processing of APP and Aβ generation. After joining FIU in 2018, he has expanded his research interests to include other neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) for which also the molecular basis for neurodegeneration is still elusive.
With the very disappointing failures of most of the clinical trials for AD based on the modulation of single target mechanisms such as Aβ, Dr. Lakshmana’s current research focus is to target complex pathways that are able to simultaneously modulate the multiple processes of neurodegenerative cascade triggering a synergistic response for a viable therapeutic approach. Since microglia activation-induced neuroinflammation or loss of synapses correlates better with cognitive dysfunction in AD than Aβ or plaque load, multifactorial and heterogeneous diseases like AD require the simultaneous modulation of multiple targets for curative treatment. Therefore, his focus now is to modulate adult hippocampal neurogenesis (AHN), endocannabinoid system (ECS), autophagy-lysosome pathway (ALP), and epigenetic pathways which are well--known to exert pleiotropic activity including not only on Aβ and hyperphosphorylated tau but also on the AHN, synaptic integrity and neuroinflammation. By modulating these pathways, Dr. Lakshmana’s long-term goal is to develop Multi-Target Directed (MTD) compounds for AD and other neurological disorders