Health Science Research Facility Room 140
Burlington, VT 05405
United States
- Ph.D, Toyohashi University of Technology, Japan
Molecular Physiology and Biophysics
Areas of expertise
Our lab investigates how molecular motors coordinate intracellular transport in neurons, with a particular focus on bidirectional motion and its disruption in neurodegenerative disease. Kinesin drives cargo transport from the cell center to the periphery, whereas dynein mediates movement in the opposite direction. Although these motors operate with opposing polarity, the mechanisms by which they coordinate to deliver cargo efficiently remain poorly understood. This challenge is further complicated by the fact that both kinesin and dynein adopt autoinhibited conformations and require activation through cargo and/or adaptor binding to enable coordinated movement along microtubules. Moreover, the two motors are functionally coupled, as perturbation of one often disrupts transport in both directions. However, the molecular mechanisms governing motor activation and bidirectional motion within kinesin–dynein complexes remain unclear.
In healthy neurons, microtubule-associated proteins such as tau stabilize microtubules and regulate cargo transport. In Alzheimer’s disease (AD), tau becomes hyperphosphorylated or mutated, weakening its interaction with microtubules, promoting aggregation into neurofibrillary tangles, and impairing axonal transport. Notably, tau preferentially inhibits kinesin over dynein. In contrast, MAP7, another microtubule-associated protein, promotes intracellular transport by recruiting kinesin, with minimal effects on dynein. These distinct regulatory roles make tau and MAP7, individually and in combination, an ideal system to test how differential modulation of motor activity influences the directionality of kinesin–dynein-driven transport in neurons.
To address these questions, we use single-molecule TIRF microscopy, optical trapping, super-resolution STORM imaging, and interferometric scattering mass spectrometry (iSCAMS). We investigate how kinesin and dynein are activated and coordinated to mediate cargo transport, the role of MAP7 in this process, and how pathological tau disrupts microtubule stability and intracellular transport. Ultimately, this work aims to link tau pathology to defects in cargo delivery to its proper destination and to identify mechanistic targets for therapeutic intervention.
BIO
Dr. Ali is an Assistant Professor in the Department of Molecular Physiology & Biophysics, where his research focuses on how opposite-polarity molecular motors, kinesin and dynein, coordinate to transport cargo, with particular emphasis on bidirectional motility and its disruption in neurodegenerative disease. Dr. Ali earned his B.Sc. in Physics from Jahangirnagar University in 1990 and his M.Sc. in Physics from Aligarh Muslim University, India, in 1993. Dr. Ali received his Ph.D. in Biophysics and Molecular Biology from Toyohashi University of Technology, Japan, in 2000. Following his doctoral training, Dr. Ali completed postdoctoral research in the Kinosita Laboratory at the Center for Integrative Bioscience, Okazaki National Research Institutes, Japan (2000–2002), where he investigated the stepwise motion of myosin V along helical actin filaments and their role in cargo transport. He then returned to Bangladesh and served as a faculty member in the Department of Physics at Shah Jalal University of Science and Technology, teaching molecular biophysics and related subjects. In 2005, Dr. Ali moved to the United States and joined the Warshaw Lab in the Department of Molecular Physiology and Biophysics at the University of Vermont, where he worked as a postdoctoral fellow and later as a research associate. In the Warshaw Lab, he continued to study the mechanisms of cargo transport driven by actin-based motors, laying the foundation for his current work on microtubule-based motor coordination.
Publications
Bio
Dr. Ali is an Assistant Professor in the Department of Molecular Physiology & Biophysics, where his research focuses on how opposite-polarity molecular motors, kinesin and dynein, coordinate to transport cargo, with particular emphasis on bidirectional motility and its disruption in neurodegenerative disease. Dr. Ali earned his B.Sc. in Physics from Jahangirnagar University in 1990 and his M.Sc. in Physics from Aligarh Muslim University, India, in 1993. Dr. Ali received his Ph.D. in Biophysics and Molecular Biology from Toyohashi University of Technology, Japan, in 2000. Following his doctoral training, Dr. Ali completed postdoctoral research in the Kinosita Laboratory at the Center for Integrative Bioscience, Okazaki National Research Institutes, Japan (2000–2002), where he investigated the stepwise motion of myosin V along helical actin filaments and their role in cargo transport. He then returned to Bangladesh and served as a faculty member in the Department of Physics at Shah Jalal University of Science and Technology, teaching molecular biophysics and related subjects. In 2005, Dr. Ali moved to the United States and joined the Warshaw Lab in the Department of Molecular Physiology and Biophysics at the University of Vermont, where he worked as a postdoctoral fellow and later as a research associate. In the Warshaw Lab, he continued to study the mechanisms of cargo transport driven by actin-based motors, laying the foundation for his current work on microtubule-based motor coordination.