10/08/2026
By Irma Silva

The Kennedy College of Sciences, Department of Biological Sciences, invites you to attend a Ph.D. proposal defense in applied biology by Karisma Sarangi titled “Trimethylamine N-Oxide as a Partial Mediator of the Cardiovascular Disease and Bone Mineral Density Axis: Epidemiological, Cellular, and Mechanistic Investigations.”

Event Details

  • Date: Tuesday, Oct. 20
  • Time: 1 – 3 p.m.
  • Location: Ball Hall 208

Committee

  • Peter Gaines, Professor, Chair, Biological Sciences, University of Massachusetts, Lowell
  • Kelsey Mangano, Associate Professor, Biomedical and Nutritional Sciences, University of Massachusetts, Lowell
  • Jeffrey Moore, Professor, Biological Sciences, University of Massachusetts, Lowell
  • Sabrina Noel, Associate Professor, Public Health, University of Massachusetts, Lowell

Brief Abstract

Cardiovascular disease and osteoporosis are two of the most prevalent chronic conditions of aging, and they are increasingly recognized as independent problems. Arteries and bone are regulated by overlapping machinery: under chronic inflammatory and oxidative stress, vascular smooth muscle cells lose their contractile identity and adopt a bone-forming phenotype directed by the very transcription factors that build bone, RUNX2 and Osterix, acting through Wnt/β-catenin signaling, and they deposit calcium-phosphate mineral similar to osteoblasts. This association is bidirectional, with low bone mass predicting cardiovascular events and cardiovascular disease predicting bone loss, yet the two diseases are still diagnosed, studied and treated in isolation. The reason is that no specific circulating signaling molecule driving both processes has been identified in humans. Trimethylamine N-oxide (TMAO), a gut microbiome-derived metabolite produced from dietary choline and L-carnitine in red meat, eggs and dairy, is a compelling candidate for that missing link: it carries the strongest cardiovascular evidence among diet-derived metabolites while remaining the least understood in bone, where emerging work suggests it suppresses osteoblast function even as it calcifies the vessel wall. A single metabolite that turns the same osteogenic program on in the artery and off in the bone would reframe these diseases as one pathway. Testing this hypothesis requires experiments that no single approach provides: human epidemiology, controlled cellular dosage and time points, and direct tests of cell-to-cell communication. This proposal brings all three together.

The work in this thesis leverages prior evidence to determine whether TMAO is a shared mediator of the cardiovascular and bone axis. Using the Boston Puerto Rican Health Study and its nested Osteoporosis Study, a population carrying a disproportionate burden of both conditions, I seek to determine:

  1. whether plasma TMAO, and exploratorily indoxyl sulfate and a composite inflammatory biomarker score, partially and independently mediate the association between cardiovascular disease and bone mineral density at the femoral neck and total hip;
  2. the dose- and time-dependent effects of TMAO across a physiologic to pathologic range on osteoblast (Saos-2) and vascular smooth muscle (T/G HA-VSMC) monocultures; and
  3. whether TMAO-primed osteoblasts amplify vascular calcification using conditioned-media and transwell co-culture systems.

Together, these studies will establish whether TMAO and its gut-microbiome pathways represent a therapeutic target for simultaneously reducing cardiovascular risk and preserving bone integrity.