Aristidis Veves, MD, ScD
Rongxiang Xu, MD, Professor of Surgery, Harvard Medical School
Director, Rongxiang Xu, MD, Center for Regenerative Therapeutics at BIDMC
Konstantinos Kounas, MD
George Theocharidis, PhD
Peng Wang, MD
I am mainly involved in ‘bench to bedside’ research. My main
research field is diabetes and its complications, with the main emphasis on
wound healing and cardiovascular disease. Approximately 90 percent of my effort
is dedicated to research, 5 percent for teaching and an additional 5 percent
for administrative and other relevant professional activities.
Translational research is a major part of my research
activities. My work mainly focuses on the interaction between neuropathy and
microvascular disease in the development of diabetic foot ulceration and the
subsequent impairment of wound healing. This work has been supported by the NIH
and nonprofit organizations. I collaborate with investigators from various
departments at BIDMC, and investigators from other institutions, such as
Brigham and Women's Hospital, to conduct additional translational research.
I conduct investigator-initiated research studies that
examine the effects of various FDA-approved medications on cardiovascular
function. These studies, although funded by industry, have been conceived,
designed, and executed by my unit and focus on possible new mechanisms through
which these medications exert their beneficial effects. I have also served as
the lead investigator and lead author in industry sponsored multicenter trials
that investigated the efficacy of new therapeutic interventions for the
management of diabetic foot ulceration.
I also run my own basic research laboratory that mainly
explores the findings of this translational research and tries to identify
mechanisms underlying the observed results. My laboratory works closely with
other laboratories in BIDMC and is funded by NIH grants. I also collaborate
with Dr. David Mooney’s laboratory at the Wyss Institute and Harvard
Engineering School and Dr. Jonathan Garlick’s at Tufts Medical School. The main
aim of our collaboration is the development of new wound-healing products. This
collaboration has resulted in NIH funding of our grant applications.
The results of my research have been published in
prestigious medical journals, including Lancet, Diabetes, and Circulation. My work, according to Google Scholar as of
December 2017, has resulted in more than 17,200 citations an h-index of 67 and
i10-index of 149.
I have also been the Director of the Rongxiang Xu, MD, Center for
Regenerative Therapeutics since its establishment in December 2015. The center
was established after a generous donation from the National Rongxiang Xu
Foundation and its mission is to further advance the treatment of patients
throughout the world with chronic wounds, burns, and other conditions resulting
from a failure of tissue repair and regeneration. As part of its mission, the
Center provides resources for the conduction of collaborative bench-to-bedside
research with investigators worldwide, as well as the education of physicians
and scientists internationally.
A major aim of our work this year was to confirm the ability of monocytes polarized to M1 and M2 in vitro, to impact healing of neuropathic wounds in diabetic animals when introduced to the wound site, and to determine the propensity of naïve monocytes derived from T1DM and T2DM to polarize to the M1 phenotype at the wound site.
A method was first developed to allow for the production of an off-the-shelf product that could be manufactured in terms of hundreds of bandages within the span of a few days. Once we had established our method for the production of bandages, RAW 264.7 murine macrophages were used to test the feasibility of these bandages as a delivery vehicle. We next optimized the isolation in vitro expansion and polarization of primary mouse monocytes. Next, we investigated whether the primary cells could be loaded and polarized into the bandages (see Figure 1).
Finally, in our fist pilot in vivo experiment, bandages loaded with cells were used to cover dorsal wounds in wild-type C57BL/6 mice. The wound closure calculations from the experiment show a clear effect of the macrophages in wound healing, especially the M1 phenotype (see Figure 2). We are currently in the process of analyzing all the histology data and are planning for a larger scale experiment with higher number of mice and using the diabetic db/db model.
In other research, we are testing the ability of biomaterials that sequentially release factors to first recruit and then direct the M2 phenotype to enhance healing in diabetic, neuropathic rodent wounds.
In the final year of the grant, we plan to complete the remaining animal experiments that will provide all necessary data that will allow us to prove or reject our primary hypothesis regarding the role of M2 macrophages. In addition, we will investigate whether our biomaterials can successfully improve impaired diabetic wound healing.
Teaching, Training, and Education
My teaching responsibilities include participation in the training of podiatry residents, supervision of the fellows and junior faculty in my laboratory, and participation in mentorship committees of junior faculty members from other units. I am also involved in educational activities of the Center for Education at BIDMC, which provides guidance to candidates for NIH K-series awards. Finally, I participated as series editor, book editor or co-editor and author in numerous textbooks. One of these textbooks (Diabetes and Cardiovascular Disease) has been already translated to the Italian language and another one (Diabetic Foot) to the Greek language.
Selected Research Support
Obstructive sleep apnea increases cardiovascular risk in type 2 diabetes; NIH, 2011-2017; Co-PI/Contact PI: Aristidis Veves, PhD, DSc
Role of Macrophages in Impaired Wound Healing in Diabetes; NIH, 2015-2018; Co-PI/Contact PI: Aristidis Veves, MD, DSc
Skin inflammatory phenotypes as biomarkers of myocardial and vascular remodeling; NIH, 2016-2021; Co-PI/Contact PI: Aristidis Veves, MD, DSc
Single cell transcriptome sequencing of diabetic foot skin; Diacomp 2017-2018; PI: Aristidis Veves, MD, DSc
Bai S, Nagai M, Koerner SK, Veves A, Sun L. Structure-activity relationship study and discovery of indazole 3-carboxamides as calcium-release activated calcium channel blockers. Bioorganic & Medicinal Chemistry Letters 2017;27(3):393-397.
Tellechea A, Pradhan-Nabzdyk L, LoGerfo FW, Veves A. Neuropeptides, Inflammation, and Diabetic Wound Healing – lessons from experimental models and human subjects. In: Veves A, Giurini JM, Guzman RJ (Eds). The Diabetic Foot: Medical and Surgical Management (Fourth Edition). Totowa, NJ: Humana Press; In Press.
Zheng Y, Shu B, Fu J, Kafanas A, Veves A. Structural and Functional Changes in Skin of the Diabetic Foot. In: Veves A, Giurini JM, Guzman RJ (Eds). The Diabetic Foot: Medical and Surgical Management (Fourth Edition). Totowa, NJ: Humana Press; In Press.
Roustit M, Loader J, Baltzis B, Zhao W, Veves A. Microvascular changes in the diabetic foot. In: Veves A, Giurini JM, Guzman RJ (Eds). The Diabetic Foot: Medical and Surgical Management (Fourth Edition). Totowa, NJ: Humana Press; In Press.
Loader J, Roustit M, Baltzis B, Veves A. Vascular Dysfunction, Inflammation, and Exercise in Diabetes. In: Reusch JEB, Regensteiner JC, Stewart K, Veves A (Eds). Diabetes and Exercise (Second Edition). Totowa, NJ: Humana Press; 2017, pp 137-150.
Reusch JEB, Regensteiner JC, Stewart K, Veves A. Diabetes and Exercise (Second Edition). Totowa, NJ: Humana Press; October 2017.
Veves A, Giurini JM, Guzman RJ. The Diabetic Foot: Medical and Surgical Management (Fourth Edition). Totowa, NJ: Humana Press; January 2018.