The Ali Lab
Hassan A. Ali, PhD, MSM
Associate Professor of Neurosurgery and Medicine
Director, High Content Screening
Welcome to The Ali Lab. We focus on therapeutic development in three main areas: neurology, oncology, and nephrology. Core activities include the development of bioassays and analytical tools for illuminating disease biology and enabling drug discovery. Projects typically involve the identification of novel druggable targets, screening campaigns, and development of promising lead compounds (small-molecules to biologics). We collaborate with academic labs and industry sponsors in the US and across the world to translate our discoveries into clinical applications.
Our Philosophy on Drug Discovery
Let Biology Lead the Way
Our lab uses state-of-the-art phenotypic screening technologies at the University of Miami, machine learning, and cutting edge biological models that span primary tissue to 3D organoids, to identify effective drug targets. 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:
Our group has led the development and implementation of idTRAX, a biotechnology that combines phenotypic screening with biochemical profiling and machine learning to identify drug targets with unprecedented speed and efficiency. We also actively develop image analysis algorithms and computational workflows to suit our discovery needs when such solutions are not readily available.
We use phenotypic screening technologies and podocytes from human origin to identify therapeutic candidates for kidney disease. We have identified a novel compound for treating diabetic kidney disease, and we are performing medicinal chemistry with our collaborators at the University of Miami and Florida International University to develop it into a lead compound appropriate for in vivo validation and preclinical development.
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. We use our knowledge of these targets to develop drug candidates for treating CNS injuries. Our candidate for spinal cord injury is currently in the preclinical development stage.
By screening compounds on cancer cells as well as normal cells, we can identify compounds that selectively kill the cancer cells while sparing normal tissue 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.
The NeuroKinome Project (NKP)
Originally trained as a kinase biochemist, Dr. Ali maintains intensive 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.
National Institutes of Health
NCATS, NINDS, NIDDK
USA Department of Defense
State of Florida
Katz Drug Discovery
W. H. Coulter Foundation
Sylvester Cancer Center