Research

The purpose of our research group is to identify causes, risk factors (positive and negative), and biomarkers of susceptibility and early diagnosis of multiple sclerosis (MS), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). Because of their progressive and disabling nature, these diseases have major adverse personal, social, and economic consequences. Prevention and early detection are critical, because there are no cures and the clinical diagnosis typically occurs after substantial and often irreversible neuronal loss, and at a time when neuroprotective interventions are probably too late to be fully effective.  At the core of our work is a series of prospective investigations that integrate genetic, biochemical, and traditional epidemiological approaches, and an interdisciplinary team including basic scientists, epidemiologists, and clinical investigators.

Current projects include, among others:

  • The investigation of the environmental determinants of MS, with focus on the possible etiological role of the Epstein-Barr virus and other infections, the adverse effects of cigarette smoking, and the protective effect of vitamin D.  This collaborative effort, with contributions from leading virologists, immunologists and geneticists, has already identified promising new targets for experimental and clinical research.  For example, our reports on the strong relation between antibody titers to the Epstein-Barr nuclear antigen 1 and MS risk have sparked interest among neuroimmunologists, who have initiated specific investigations on T cell responses to this protein in MS.  On the other hand, our recent finding that high circulating levels of vitamin D are a strong negative marker of MS risk and progression has substantial translational implications for MS prevention and treatment. Among the ongoing projects is a systematic investigation on the role of salt intake in MS progression.

 

  • The investigation of the role of on lifestyle, diet and biomarkers in determining PD risk. This project includes the assessment of non-motor signs of prodromal disease, and collaborations with molecular neuroscientists and clinical investigators for the discovery of novel biomarkers.in a set of studies that bridges epidemiology and clinical trials research. One of the most important discoveries of this work is that of urate in serum is an important predictor of PD risk and clinical progression.  The identification of urate as the first molecular predictor of disease progression has provided the rationale for a phase 2 trial recently completed and for an ongoing NIH-funded phase 3 trial of urate elevation of which I am co-PI. Similarly, there is growing interest in the translational implications of other epidemiological findings, most notably the possible protective effects of caffeine, ibuprofen, and physical activity.  We are currently conducting a large metabolomics investigation to identify novel biomarkers of PD risk.

 

  • A consortium of large longitudinal investigations of ALS to determine the potential protective effects of vitamin E, carotenoids, and n-3 fatty acids intake.  This project includes a biomarker component targeting serum urate, carotenoids, and lipids, as well as a metabolomic analyses in blood samples collected from individuals with ALS before the disease onset.  This project stands to provide novel insights on the etiology and risk factor for ALS and ALS progression, and may lead to novel approaches to prevention and treatment.

 

  • We have more recently started to investigate the role of diet in cognitive decline.  Relying on 30 years of data collected among ~ 50,000 men in the Health Professionals Follow-up Study we are systematically searching for aspects of diet that predict the earliest sign of memory loss and cognitive problems.