Current Trainees

Fatima El Adili, MD

(July 2019-Present)
Mentor: Andrea Bujor, MD, PhD

Trainees Research Project and Progress
SSc is an autoimmune connective tissue disease in which endothelial dysfunction, inflammation and fibroblast activation lead to skin and internal organ fibrosis. This disease carries the highest mortality rate amongst autoimmune diseases, and is frequently complicated by heart involvement. The goal of Dr. Adili’s research project is to determine the role of monocytes and macrophages in SSc cardiomyopathy (CMP). We have recently discovered that the transcription factor Fli1 is expressed at low levels in SSc monocytes. We have deleted Fli1 via siRNA in human Mo/Mø, and via Cre mediated recombination in LysMCre/Fli1fl/fl mouse cells. Our preliminary data shows that deletion of Fli1 in Mo/Mø via si-RNA, or via Cre-mediated recombination using LysMCre mice (LysMCre/Fli1fl/fl), results in upregulation of several pro-inflammatory and chemotactic genes.
To expand on these studies we will leverage an existing repository of human heart tissue from SSc patients and controls to validate the findings from LysMCre/Fli1fl/fl mice. The LysMCre/Fli1fl/fl mice have enhanced inflammatory infiltrates, heart fibrosis and diastolic dysfunction; SSc-CMP will have Mø with low Fli1 that will display a similar phenotype to the LysMCre/Fli1fl/fl heart Mø. This project is innovative because it tests the novel concept that low Fli1 in SSc-Mo/Mø contributes to organ fibrosis, via a comprehensive approach using human samples and conditional mutagenesis and lineage tracing in mice. The significance of this work lies in the potential to identify Fli1 as a new therapeutic target for SSc CMP, which has no current treatment options and high mortality.
Conference Presentations

Poster presentation at Evans Days Boston University October 18 2019, Boston, MA.

Andreea Bujor, Fatima El adili; Arshi Parvez Olivia Heutlinger; Giuseppina Farina, Flora Sam. Periostin is increased in scleroderma cardiomyopathy. Arthritis Research and Therapy, 2019 November ARRT-D-19-00749 – Under review
Trainee designed and conducted experiments, analyzed data, and reviewed the final manuscript.

Clive Baveghems, pic clive

Structural Remodeling of HDL Proteins in Patients with Diabetes Mellitus

(July 2017-present; Olga Gursky, PhD; mentor)

Dysregulation of plasma high-density lipoproteins (HDL) is implicated in diabetes mellitus and cardiovascular disease. Structurally, HDL forms a heterogeneous population of mature spherical and nascent discoidal particles 8-12 nm in diameter, consisting of lipids and surface apolipoproteins. The major HDL proteins are apoA-I and apoA-II. ApoA-I provides a structural scaffold and a functional ligand on the particle surface, and apoA-II stabilizes the HDL particle and modulates its functions. We are probing the structural and compositional changes that occur in these lipoproteins due to the onset of diabetes. Our goal is to identify and investigate novel biochemical mechanisms involved in HDL remodeling associated with disease. In ongoing studies, blood samples were collected from cohorts of patients who were normolipidemic and normoglycemic (NL-HDL), diabetic patients who maintained good glycemic control due to medication (GC-HDL), and patients with poor glycemic control prior to receiving medication (PC-HDL). Each cohort consists of 20-25 pooled samples that were frozen at -80ºC immediately after fractionation. Lipoprotein fractions are studied for biochemical composition, structure and stability by using circular dichroism spectroscopy, SDS and native gel electrophoresis and Western blotting, and negative staining electron microscopy. Current results suggest an increased degradation rate of HDL proteins in the PC-HDL group when compared to GC-HDL or NL-HDL. Recent Matrix Assisted Laser Desorption Ionization Time of Flight mass spectrometry (MALDI-TOF MS) data confirm the absence of any post-translational modifications in all major apolipoproteins between the normal and diabetic group. Furthermore, irrespective of the cohort, there is an overall correlation between increased triglyceride content and loss in protein secondary structure and stability. We are currently expanding studies of these patient-derived samples with the ultimate goal of elucidating the biochemical, biophysical and structural underpinnings for changes in lipid and apolipoprotein metabolism associated with diabetes and cardiovascular disease.

Poster Presentation:

Clive Baveghems; Shobini Jayaraman; Olga Gursky, Structural Remodeling of HDL Proteins in Patients with Diabetes Mellitus: Evans Department of Medicine Research Days 2017, Boston University School of Medicine, Boston MA, 2017.


Shobini Jayaraman; Clive Baveghems; Olivia R. Chavez; Andrea Rivas-Urbina; Jose Luis Sánchez-Quesada; Olga Gursky, Effects of triacylglycerol on the structural remodeling of human plasma very low- and low-density lipoproteins. BBA – Lipids (under review).

Baveghems, C. L.; Anuganti, M.; Pattammattel, A.; Lin, Y.; Kumar, C. V., Tuning Enzyme/α-Zr (IV) Phosphate Nanoplate Interactions via Chemical Modification of Glucose Oxidase. Langmuir 2018, 34, 480-491.


Structural Remodeling of High-Density Lipoproteins in Patients with Diabetes Mellitus, Clive L. Baveghems, Symposium organized by the Division of Colloid and Surface Chemistry, 256th American Chemical Society meeting, Boston MA 2018.

Parul Chaudhary, MBBS, PhD

(July 2019 – Present)
Mentor: Richard D. Wainford, PhD

Trainees Research Project and Progress
Over 90% of US adults consume excess dietary salt exceeding 3.4g/day. High salt intake impacts central sympathetic outflow to the kidneys which modulates renal sodium excretion (natriuresis) and blood pressure (BP) regulation. This, in conjunction with the salt sensitivity of BP, which is estimated to exist in 50% of hypertensive individuals, can lead to salt-sensitive hypertension. The goal of my research is to understand the mechanisms underlying the pathophysiology of salt-sensitive hypertension. In hypertensive salt-sensitive and normotensive salt-resistant rat models using central drug infusion, brain microinjection, immunohistochemistry, in-situ hybridization and retrograde neuronal tracing techniques we are investigating the impact of PVN Gαi2 protein on 1) neuronal activation in the PVN of the hypothalamus in response to acute and chronic sodium challenges, and 2) temporal changes in central inflammation and microglial activation in the PVN in response to chronic high salt intake. These result will help elucidate the role of PVN Gαi2 proteins in the neural control of BP and sympathoexcitatory mediated central inflammation in salt-sensitive hypertension. We have a manuscript in preparation detailing the cellular phenotype of Gαi2 expressing neurons in the PVN and have published and initial manuscript detailing the role of PVN Gαi2 proteins in mediating inflammation in the PVN during high salt intake.
Additionally, using human clinical plasma samples from patients in which are able to identify salt sensitive versus salt resistant subjects from the DASH-2 Sodium trial (obtained via the NIH BioLINCC resource), we have conducted an assessment of the impact of urinary sodium to potassium ratios with both hypertension and the salt sensitivity of blood pressure and we are currently conducting metabolomic and lipidomic profiling of these same samples. These results may provide potential biomarkers or a “physiological signature” that can help predict the salt sensitivity of BP in human subjects meeting an unmet clinical need.

Oral Conference Presentations:
Increased Urinary Potassium Excretion Does Not Associate With Reduced Systolic Blood Pressure in the Dietary Approaches to Stop Hypertension Sodium Trial. American Heart Association Hypertension Council Hypertension Sessions, September 7 2019, New Orleans, LA.
Reduced Urinary Sodium to Potassium Excretion Ratio Does Not Associate With Reduced
Systolic Blood Pressure in Dietary Approaches to Stop Hypertension Sodium Trial, Evans Department of Medicine Research Days, October 18 2019

Moreira, Jesse D., Parul Chaudhary, Alissa A. Frame, Franco Puleo, Kayla M. Nist, Eric A. Abkin, Tara L. Moore, Jonique C. George, Richard D. Wainford. “Inhibition of microglial activation in rats attenuates paraventricular nucleus inflammation in Gαi2 protein‐dependent, salt‐sensitive hypertension.” Experimental Physiology 2019 104:1892-1910
Trainee designed and conducted experiments, analyzed data, and reviewed the final manuscript.

Parul Chaudhary, Richard D. Wainford. “Association of urinary sodium and potassium excretion with systolic blood pressure in The Dietary Approaches To Stop Hypertension Sodium Trial.” Journal of Human Hypertension – Under review
Trainee designed and conducted experiments, analyzed data, drafted the paper and reviewed the final manuscript.

Career Development Activities:
Scientific Writing Course. Department of Anatomy and Neurobiology, Boston University School of medicine, MA.

Vladimir Mastyugin pic vlad

Novel PLA2g6/Ca2+ – targeting approach for prevention of age and/or HFHS diet-induced aortic stiffening.

(July 2017- present; Victoria M. Bolotina, PhD; mentor)

Aging or high fat/high sucrose (HFHS) diet-induced aortic stiffening is one of the major risk factors of cardiovascular disease. However, the mechanism(s) underlying this pathology are poorly understood, and there is currently no prevention or treatment for this pathological condition.

Dr. Mastyugin’s studies are focused on the two cellular processes in vascular smooth muscle cells (SMC), inhibition of which can produce the opposite effects on aortic stiffness:

  • Bolotina’s lab discovered that there is no arterial stiffening in the aorta of the mice with impaired Ca2+ signaling function of the multifaceted phospholipase A2 group 6 (PLA2g6) enzyme,
  • Seta discovered increased stiffening in aorta of the mice that lack BCL11b gene, a C2H2-type zinc finger protein, which exact function is yet to be determined.

These important discoveries pointed to the brand new mechanisms involved in this vascular pathology and opened possibilities for testing new approaches to prevent or reverse aortic stiffening caused by age and/or by HFHS (American) diet.

My research is  focused on in vitro testing of a new molecular approach specifically targeting PLA2g6/Ca2+ signaling, and the possibility for its in vivo application for prevention or reversal of aortic stiffening in mouse models. To mimic Ca signaling deficit that we found in SMC from PLA2g6ex2KO mice that are resistant to aortic stiffening, (a) I am testing the role of specific PIN domain in PLA2g6(L) plasma membrane localization, (b) creating PLA2g6-specific peptides that can affect localization and/or activity of PLA2g6, (c) testing the effects of such peptides on Ca signaling and other properties of vascular SMC.  The overall goal of these studies is to develop novel small peptide PLA2g6-targeting approach to achieve SMC-specific reduction in PLA2g6-dependent Ca2+ signaling, which can mimic its deficit in ex2KO mouse model, and to protect aorta from HFHS stiffening, or to reverse this pathology in two different mouse models (WT mouse fed with HFHS diet, and/or BCL11b KO mice).


Manuscripts in preparation:

Yen A., Shim J.W., Nipa F., Mastyugin V., Bachschmid M., Mostoslavsky G., Pirot S., Mannoury-la_Cour C., Milan M.J., Bolotina V.M. Restoration of PLA2g6-dependent Ca2+ signalling in dopaminergic neurons as a new strategy to stop progression of Parkinson’s disease.

Educational Enrichment:

Attended Webinars on New technologies.

Meetings attendance:

  • Developments in Protein Interaction Analysis (DiPIA), Boston, MA (June 17-20, 2018)
  • Redox Metabolism. A Mini Symposium by the Clinical Metabolic Research Collaborative Evans Center Pre-ARC, BNORC, and Whitaker Cardiovascular Institute (Wednesday, May 2, 2018)


  • Mastyugin V.,  Yen A., Zhou Q., Shim J.W., Seta F., and Bolotina V.M. Targeting PLA2g6/Ca2+ signaling for protection against human diseases. Evans Department of Medicine Research Days, October 11-12, 2018.Research Poster Session.
  • Mastyugin V., Yen A., Zhou Q., Shim J.W., Seta F., and Bolotina V.M. Novel PLA2g6/Ca2+-targeting approach for prevention of age and/or HFHS diet-induced aortic stiffening. Evans Department of Medicine Research Days, October 12-13, 2017.Research Poster Session.

Manuscripts in preparation:

  • Shim J.W., Nipa F., Mastyugin V., Yen A., Seta F., Bolotina V.M. Impairment of PLA2g6-depedent Ca2+ signaling in vascular smooth muscle protects against arterial stiffening.

Christina M. Ward, PhD

(August 2019 – Present)
Mentor: Katya Ravid, PhD

Trainees Research Project and Progress
Platelets play a pivotal role in the maintenance of normal hemostasis. Circulating platelets directly impact the development of thrombosis and contributes to underlying cardiovascular diseases such as atherosclerosis. Therefore, understanding platelet production from the megakaryocyte (MK) has broad applications in the treatment of cardiovascular disease. The focus of her research project is to gain a greater understanding of mechanical stimuli in the bone marrow that contributes to megakaryocyte development. The mechanosensitive ion channel, PIEZO1, modulates cellular mechanical stimuli from the extracellular matrix (ECM). Megakaryocyte differentiation and proplatelet formation depend on components of the bone marrow ECM, we hypothesize that PEIZO1 activation regulates the ability of MK cells to respond to the ECM present in the bone marrow niche. I have demonstrated that pharmacological activation of the PIEZO1 channel by PIEZO1 selective agonist, YODA1 increases the percentage of MKs present in primary murine bone marrow cultures. PIEZO1 activation by YODA1 reduces the overall ploidy of the MKs in this culture system. Therefore, it is possible that PIEZO1 activation acts as a proliferative signal in MKs. Further mechanistic work is being conducted to this end.

Liu, L., Zhu, X., Yu, A., Ward, C.M., & Pace, B.S. (2019). Feature article: δ-Aminolevulinate induces fetal hemoglobin expression by enhancing cellular heme biosynthesis. Experimental Biology and Medicine, 244(14), 1220–1232.
Trainee designed and conducted experiments, analyzed data and reviewed the final manuscript.

Li B, Zhu X, Ward CM, et al. MIR-144-mediated NRF2 gene silencing inhibits fetal hemoglobin expression in sickle cell disease. Exp Hematol. 2019;70:85–96.e5. doi:10.1016/j.exphem.2018.11.002
Trainee designed and conducted experiments, analyzed data and reviewed the final manuscript.

Beatriz Ferran Perez, PhD

Redox therapy approaches to improve ischemic limb vascularization

(T32 postdoctoral trainee since July-2018 to present; Mentor: Reiko Matsui, MD)

Many diseases are associated with increased levels of reactive oxygen and nitrogen species, however it is demonstrated that certain levels of oxidants are necessary to promote ischemic angiogenesis. Oxidants transduce angiogenic signaling by post-translational protein thiol modifications. The reaction of protein thiols with cellular glutathione (GSH) renders stable protein-GSH adducts (S-glutathionylation), which are able to alter the protein function. Protein-GSH adducts are reversed by glutaredoxin-1 (Glrx), a cytosolic enzyme that can inhibit angiogenesis by modulating several proteins including HIF-1a. We found that Glrx inhibition promotes angiogenesis via HIF-1α stabilization.
My work is focused on redox-regulation of ischemic vascularization related with aging and type 2 diabetes. Diabetic patients have a worse blood flow recovery in response to ischemia comparing with non-diabetic subjects. Since Glrx expression regulates the ischemia-induced angiogenic responses, my research interest is to find out the molecular mechanisms by which modulating Glrx activity/expression in the skeletal muscle may improve vascular recovery after hindlimb ischemia, and to propose an effective therapy. To achieve this goal, my main objectives are A) generate skeletal muscle-specific Glrx KO mice by using the Cre-Lox system and by adeno-associated virus (AAV) injection; B) contribute to establish an AAV production and purification method for in vivo studies; and C) as a therapeutic approach, apply AAV-mediated Glrx inhibition to poor vascularization models like diabetic mice and middle-age female mice.

Work progress:
A) The colony of muscle-specific Glrx KO mice is already growing and I expect to have the first animal cohort in three months.
B) I contributed to optimize an affordable protocol for producing and purifying AAV in our laboratory, resulted in a manuscript submitted to Scientific Reports, now in the revision process. Tests of the viral suspensions indicated that AAV particles can be used to inhibit Glrx expression in vivo and in vitro. I am working now in the design of the viral DNA to decrease the inflammation caused by the AAV intramuscular injection.
C) I performed pilot experiments inducing hindlimb ischemia in middle-age mice and confirmed that females show worse blood flow recovery than males. Also, I am working on the method to detect Glrx target proteins in skeletal muscle samples by immunoprecipitation with anti-GSH antibodies.


  • Poster presentation in the Evans Research Day. October 11, 2018 (Boston University School of Medicine, Boston)
  • Poster presentation in the 25th Annual Conference of the Society for Redox Biology and Medicine (SfRBM). November 14-17, 2018 (Chicago)
  • Work-in-Progress presentation in the WCVI Seminar Series. January 29th, 2019.

Workshop attendance:

Pre-meeting workshop “Oxidative Stress and Signaling: Methods, Mechanisms, and Therapeutics”. November 14th, 2018 (Chicago), at the 25th SfRBM Annual Conference.


  • Weinberg EO, Ferran B, Tsukahara Y, Hatch MMS, Han J, Murdoch CE, Matsui R. “IL-33 induction and signaling are controlled by glutaredoxin-1 in mouse macrophages.” PLoS One. 2019 Jan 25;14(1):e0210827. (PMID: 30682073)
  • Toyokazu Kimura, Beatriz Ferran, Yuko Tsukahara, Qifan Shang, Suveer Desai, Ivan Luptak, David Richard Pimentel, Takeshi Adachi, Yasuo Ido, Reiko Matsui, Markus Bachschmid. “Production of adeno-associated virus vectors for in vitro and in vivo applications”. Manuscript in revision, submitted to Scientific Reports.

Sana Majid, MD

Determining Cardiovascular Injury due to the Use of Novel Tobacco Products

(July 2018 – present; Naomi M. Hamburg, MD, MS)

Electronic cigarettes (e-cigarettes) are marketed as safer alternatives to combustible tobacco products; however, whether e-cigarettes are a harm reduction tool with reduced cardiovascular (CV) toxicity is unknown. Dr. Majid seeks to identify e-cigarette product characteristics associated with CV injury. Specifically, Dr. Majid will evaluate the effects of Juul, the top selling e-cigarette in the US, on endothelial cell phenotype. She hypothesizes that Juul e-liquids will induce endothelial cell toxicity and that toxicity will vary based on the flavoring additives and nicotine levels. In order to test this hypothesis, she will evaluate the effects of available e-liquids at varying concentrations on cellular viability, nitric oxide production, and oxidative stress in commercially available endothelial cells. She has learned how to perform the assays and will start cell exposures in the coming weeks. Dr. Majid has additional work evaluating the relations of plasma lipids with e-cigarette use in the Cardiovascular Injury due to Tobacco Use (CITU) cohort. She hypothesizes that specific volatile organic compounds may mediate the association of alterations in plasma lipids associated with e-cigarette use. She has written the analytic plan and has begun the analyses. Through her efforts, Dr. Majid will identify e-cigarette product characteristics associated with cardiovascular toxicity. Her work will lend additional support for regulations on product characteristics associated with cardiovascular injury such as setting permissible limits on flavoring additives.


AHA Tobacco Regulation and Addiction Center (A-TRAC) 2.0 Fellowship (2018-2020)

Meeting attendance:

American Heart Association (AHA) Scientific Sessions 2018, Chicago, IL (November 10-12)

Poster presentations:

S. Majid, J. L. Fetterman, R. J. Keith, R. M. Weisbrod, M. Holbrook, M. M. Stathos, R. Breton-Romero, R. Bastin, B. Feng, R. M. Robertson, A. Bhatnagar, N. M. Hamburg. The Impact of Combustible and Electronic Cigarette Use on Vascular Health: An Observational Study. Boston University Evans Department of Medicine Research Days (October 11).


Introduction to Statistical Computing – Boston University, Boston, MA (Fall 2018)

Joel May, PhD

Identifying the mMolecular Methods mechanisms by which of BCL11B rRegulatestion of Arterial Stiffnessarterial function

(July 2018- present; Francesca Seta, PhD; mentor)

Loss of compliance in elastic arteries, also known as Increasing levels of arterial stiffening,ness are is associated with an increased risk of cardiovascular events disease such as atherosclerosisheart failure, cardiac infarction and stroke. As these diseases are the amongst the top causes of death in the developed world, understanding and controlling risk factors at an early stage can help alleviate the burden of these diseases in an increasingly aging and overweight/obese population. A genome wide association study (GWAS) searching for loci associated with arterial stiffness revealed a series of high risk single nucleotide polymorphisms (SNPs) within a distal enhancer of the C2H2 zinc finger transcription factor BCL11b.
Based on the scientific premise of the GWAS findings, Since theDr Seta’sn, laboratory started to investigate a potential role of Bcl11b in regulating arterial function. BCL11B has been shown to have a role in controlling arterial stiffness. We found that mMice carrying a vascular smooth muscle (VSM) specific knock out of the Bcl11b gene (BSMKO) show an increased pulse wave velocity (PWV), the gold standard measure of arterial stiffness, as well as decreased transcription of VSM contractile proteins mMyosin heavy chain 11 (MYH11) and sSmooth muscle α-actin (αSMA). Moreover, BSMKO mice given the hypertensive agent angiotensin-II (aAng II) for 2 weeks develop aortic aneurysms. BCL11B is primarily known as a transcriptional repressor and has been shown to associate with the histone deacetylase sSirtuin-1 (SIRT1); however, in some contexts, BCL11B can act as a transcriptional activator through its association with the histone acetyltransferase p300.

Dr. May’s work consists of trying to finThe major goal of my project is to determined how BCL11B regulates VSM gene expression. Firstly, I started to examine whether through chromatin immunoprecipitation (ChIP). This technique will determine whether BCL11B binds directly to the promoter regions of the VSM genes Myh11, αSma and Sm22, as well as characterize the histone tail modifications (acetylation and methylation) around at these geneloci usings. chromatin immunoprecipitation assays (ChIP).

Secondly, I am developing tools to examine whether the distal enhancer with SNPs highly associated with arterial stiffness in GWAS regulates Bcl11b expression in VSM cells and aortas. I am currently generating a reporter plasmid containing the enhancer and Bcl11b promoter to test our hypothesis.
A third part of my project is to characterize the mechanical properties of WT and BSMKO aortas wWith collaborator Dr Bellinis at North Eastern University. Dr. May has also attempted to evaluate the mechanical limits of the aorta from wild type and BSMKO mice. We are testing the hypothesis that BSMKO aortas are structurally impaired due to decreased contractile proteins and this leads to aortic aneurysm development when exposed to increased hemodynamic load such as angII-hypertension. From this they hope to observe whether the increase in internal pressure causes the walls of BSMKO aortas to breach more easily. This will be achieved through measuring the axial and circumferential stresses of WT and BSMKOthe aortas with the biaxial the Myographmechanical testing system developed by Dr. Chiara Bellini.
By understanding the mechanisms through which BCl11b regulates aortic stiffnessvascular smooth muscle gene expression and function, we seek to identify druggable targets that can be used to therapies targeting these molecular pathways can be developed to preventatively treat arterial stiffness and other cardiovascular diseasesaortic aneurysm.

Manuscript in Preparation:

  •  Bcl11b is a Newly Identified Regulator of Vascular Smooth Muscle Phenotype and Arterial Stiffness.
    Jeff Arni Valisno, JoelMay,Pavania Elavalakanar, Christopher Nicholson, Kuldeep Singh, Dorina Avram, Richard A. Cohen, Gary F. Mitchell, Kathleen G. Morgan, Francesca Seta
  • Vascular smooth Muscle BCL11B is crucial for aortic wall integrity in respposonse to angiotensin II- hypertension.
    Joel May, Jeff Arni Valisno, Erika Minetti, Sabreea Parnell, Yasmen Farra XXX, Richard Cohen, Gary Mitchell, Chiara Bellini, Francesca Seta