For Alzheimer's and Brain Awareness Month, ANA interviewed Dr. Dongming Cai, an Associate Professor in the Department of Neurology at the Icahn School of Medicine at Mount Sinai and Staff Physician for James J. Peters VA Medical Center.
What does the public need to understand about Alzheimer's disease that it often doesn’t?
Oftentimes, the public doesn’t understand why developing effective therapies for Alzheimer’s disease (AD) is difficult. The challenges of AD research are due to heterogeneity of patient population and multifaceted disease mechanisms.
How are treatment options for AD different today from 10 years ago?
Current paradigms of AD drug development design have been shifted from a single-target approach (primarily amyloid-centric) to developing drugs targeted at multiple disease aspects. In addition, research now also focuses on preventive strategies at early stages of disease development rather than treating AD at later stages of disease progression.
What promising research is poised to change the standard of treatment for AD?
Using a combination of genome-wide association, linkage analysis, whole genome/exome sequencing, and rigorous data mining approaches, several genetic loci and risk factors associated with sporadic AD have been identified, suggesting that perturbations in the endosomal and lysosomal pathway, lipid metabolism, and immune response system substantially contribute to AD pathogenesis. These research advances have shaped our understanding of AD pathogenesis, the future design of clinical trials, and opening a new era of innovative Alzheimer’s disease research.
What work is your lab undertaking to move understanding or treatment for AD forward?
The ultimate goal of my laboratory studies is to translate the current understanding of disease mechanisms into development of novel diagnostic and therapeutic strategies for AD. Our work focuses on studying the regulation of phospholipid composition and metabolism, as well as protein trafficking in AD pathogenesis. Our recent findings uncover novel roles for modulating brain phosphoinositol levels through its key degrading enzyme in AD therapies (e.g., amyloid clearance, tau pathology, lysosome dysfunction and ApoE4 pathogenic nature).
We recently uncovered a novel role of a micro-RNA in regulating brain phospholipid pathways that contribute to the ApoE4-induced susceptibility of developing AD. Data from these studies implicate new therapeutic options for AD that target ApoE4 pathogenic nature through miRNA modulation (Mol Psych, in press). Our current research projects focus on better understanding the molecular mechanisms underlying ApoE4 detrimental effects in AD and other neurological disorders, as well as developing preclinical candidates and new chemical scaffolds for AD therapies. Other projects in the lab attempt to explore the interaction between ApoE4 and sex in AD, understand selective regional vulnerabilities in AD, investigate cell-type specific changes in AD, as well as ApoE2 protective effects against AD.
How has the ANA supported your career and/or work in this area?
Since joining the ANA as a junior member in 2016, I have been generously supported by travel awards to attend the 141st and the 142nd Annual ANA meetings, where I was provided with opportunities to present our research work and network with other investigators in the AD research field. I was invited to be a co-chair of the Traumatic Brain Injury (TBI) Special Interest Group (SIG) of the annual meeting in 2018, and then a chair of the TBI SIG for the annual meeting in 2019. I was the member of the Scientific Program Advisory Committee of the ANA from 2017-2020. These opportunities have allowed me to exercise the skills required for leadership roles and develop stronger organization skills that are critical for my career development.