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Welcome to the Ali Lab
We create and deploy biotechnologies to advance medical knowledge and enable drug discovery. By leveraging machine learning/AI and robitics, we maximize the utility of our experimental data, minimize assumptions, and let biology guide us to the answers. Projects typically involve screening campaigns, identifying novel drug targets, revealing mechanisms of action, and generating promising therapeutic candidates. We collaborate with academic, industry, and federal partners to translate and apply our discoveries.
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Our Approach to Discovery
Let Biology Lead the Way
Our lab uses state-of-the-art phenotypic screening technologies, machine learning, and high quality biological models (primary tissue to 3D organoids) to identify effective drug targets, MOAs, and NCEs. We then use knowledge of these targets to help design effective drugs, including ones that simultaneously engage multiple targets (polypharmacology) to maximize efficacy and improve safety. This highlights the important role of academic drug discovery, where academicians have more room to innovate and explore novel approaches. It also underscores the importance of academia-industry partnerships to then translate those innovations into clinical applications. You can read more about the topic in this review by Dr. Ali:
Platform Technologies
We developed and implemented idTRAX, a biotechnology platform that combines phenotypic screening with biochemical profiling and machine learning to identify drug targets with unprecedented speed and efficiency (1, 2, 3). We also actively develop image analysis algorithms and computational workflows to suit our discovery needs when such solutions are not readily available.
Nephrology
We use phenotypic screening technologies and podocytes from human origin to identify therapeutic candidates for kidney disease. We have identified a novel compound series for treating diabetic kidney disease, which appear to work by inducing lipophagy (7). These compounds showed promising in vivo activity and are currently in preclinical development.
Neuroscience
We have identified drug targets for modulating various biological processes related to healing of the central nervous system (CNS) following injury, including processes related to nerve regeneration and neuroinflammation (4, 5, 6). We use our knowledge of these targets to develop drug candidates for treating CNS injuries. Our candidate for spinal cord injury is currently in preclinical development.
Oncology
By screening compounds on cancer cells as well as normal cells, we can identify ones that selectively kill the cancer cells while sparing normal cells. We then use our idTRAX platform to identify drug targets that selectively sensitize cancer cells. This is of major importance for developing effective oncology drugs that do not have broad toxicity and do not further reduce the function of organs already burdened by the presence of a tumor. Here's an example from applying this approach to Diffuse Large B Cell Lymphoma (DLBCL), which led to the identification of a novel drug target which we are currently pursuing for developing a single-agent therapeutic for this deadly disease (8).
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The NeuroKinome Project (NKP)
Initially trained as a kinase biochemist, Dr. Ali maintains strong research interest into this family of drug targets. Kinases regulate most - if not all - aspects of cell biology, and mounting evidence demonstrates that kinases critically mediate both degenerative and regenerative CNS pathologies. The kinome represents the second largest drug target family (after GPCRs), despite the fact that only ~10% of all kinases are currently targeted by FDA approved drugs. Utilizing the kinome to treat the CNS therefor remains a novel idea that is yet to be exploited.
As a member of the Miami Project to Cure Paralysis (MP), our lab collaborates with others in the MP to develop innovative technologies that could accelerate the identification of kinase drug targets. We also develop cell-based assays that can be readily deployed for probing mechanisms related to nerve regeneration and CNS immunomodulation. The NKP is a multi-lab collaboration between Dr. Ali's group and several others at the MP (Lemmon/Bixby, Lee, Brambilla). The overall goal is to increase the translational potential of research into therapeutics for CNS repair.
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Funding support
NIH
National Institutes of Health
NCATS, NINDS, NIDDK
DoD
USA Department of Defense
SoF
State of Florida
IND
Industry Sponsors
UM
Miami Project
Katz Drug Discovery
Wallace H. Coulter Center
Sylvester Cancer Center
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