Current Research and Scholarly Interests
According to our recent findings and those of others, innate immune responses in humans and other mammals involving infection-, injury-, or stress-related dynamic imbalances between particular, immunomodulatory host defense peptides we study, and pro-amyloid / fibrillogenic peptides including ABeta and IAPP, may play a role in the poorly understood etiology of chronic / progressive plaque diseases, including diabetes type II melittus, atherosclerosis and Alzheimers dementia. All of these diseases involve dysbiosis, senescent/dystrophic cells, inflammation, and "proteopathies" or plaque accumulation; and can be complicated by infection by a variety of pathogens—bacterial, viral, and fungal.
The latter disease, Alzheimers dementia, is in need of a major breakthrough in fundamental understanding, more than almost any human disease currently under study. Of a total of 450+ clinical trials initiated by Pharma towards the development of Alzheimer's treatments over the past 16+ years, almost all of these trials have failed (save two recently: Biogen's Aduhelm, and Eisai's Leqembi, which can only slow the rate of cognitive decline by 25-30% at best, and which have significant side effects). There is no current effective pharmaceutical treatment to fully halt or reverse the development of dementia. Obviously, the most fundamental ideas for what drives Alzheimers must be flawed or incomplete.
Until recently Alzheimers disease was believed to be the sixth leading cause of death in the United States, according to the Centers for Disease Control and Prevention (CDC). But in March 2014, new research published in Neurology suggested that Alzheimers may actually be responsible for as many deaths each year as heart disease or cancer—the two leading causes of death in the U.S.—due to issues, in hospitals, of improper prior determinations of underlying causes of death in the elderly.
My lab is developing and testing novel mechanistic hypotheses of Alzheimers etiology, based on recent, unique molecular biophysical observations of pro-amyloid and innate immune peptides. We are also studying linkages to certain chronic infections and innate immune dysregulation.
Increasing numbers of epidemiological and co-morbidity studies indicate that multiple, progressive degenerative diseases, all involving plaque deposition in various body compartments, are linked. For instance, some researchers have begun to refer to Alzheimers Disease as "Diabetes Melittus Type III". We seek, with current research projects, to sleuth out the shared molecular biophysical and physiological bases for these emerging linkages, so that these conditions may be prevented.
(Note: Succinct, exemplary summaries of these fascinating epidemiological / comorbidity linkages are found, for instance, in the following papers: "The ‘psoriatic march’: a concept of how severe psoriasis may drive cardiovascular comorbidity", Experimental Dermatology (2011) 20, 303–307; "Circle of Willis atherosclerosis: association with Alzheimer’s disease, neuritic plaques and neurofibrillary tangles", Acta Neuropathol (2007) 113:13–21; "Increased prevalence of the metabolic syndrome in patients with moderate to severe psoriasis", Arch Dermatol Res (2006) 298: 321–328; "Association of Alzheimer disease pathology with abnormal lipid metabolism", Neurology (2011) 77;1068).
