Current Trainees

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.


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.

Jason Nasse Ph.D. Head shot

Regulatory and Signaling Mechanism of the Pleiotropic Protein Klotho

(March 2017-present; Carmela Abraham, Ph.D.; mentor)

Aging is one of the major causes of cardiovascular and neurodegenerative diseases, which can share dysfunctions of some major cellular processes. In recent years the anti-aging protein Klotho has garnered much attention for its association with, and ability to ameliorate age-related diseases including, atherosclerosis, vascular calcification, and age-related cognitive decline.  The causes of these diseases involve diverse pathways and mechanisms.  However, increased systemic inflammation and oxidative stress is a common phenomenon among them and contributes to disease progression and other co-morbidities.  The pleiotropic protein Klotho can mitigate systemic inflammation and oxidative damage both in the periphery and in the brain.  Klotho expression is decreased as both a function of age and in chronic diseases such as Alzheimer’s, Multiple Sclerosis, and chronic kidney disease.  While the effects of increased Klotho levels are well documented, the mechanisms underlying Klotho signaling and genetic regulation are largely unknown.  The focus of Dr. Nasse’s work is identify receptors that interact with Klotho to produce anti-oxidant and anti-inflammatory proteins and to discover transcription factors that regulate Klotho expression.  In collaboration with BU researchers he had identified more the 40 TFs that interact with the Klotho promoter using an enhanced yeast-1 hybrid assay and is currently testing these in mammalian cells lines expressing Klotho.  In addition, Dr. Nasse is employing the novel proximity labeling protein APEX-2 to identify Klotho binding partners in the cell membrane.  By uncovering the signaling and regulatory mechanisms of Klotho potential drug targets and therapeutics may be developed for treating neurodegenerative and cardiovascular diseases.

Meeting attendance:

The Society for Neuroscience Annual Meeting, Washington D.C. (November 11-15)

BU Pharmacology & Experimental Therapeutics – Pfizer Symposium on Emerging Technologies, Boston, MA; (May 1)

Educational Enrichment:

Drug Discovery & Development (D3) Project Simulation, Presented by Novartis Institutes for Biomedical Research (May 30-31)


Zeldich, E., Chen,CD., Boden, E., Howat, B., Nasse, JS., Zeldich, D., Lambert, AG., Yuste A., Cherry, JD., Mathias, RM., McKee, AC., Hatzipetros,T.  and Abraham, CR.  Klotho is neuroprotective in the SOD1G93A mouse model of ALS, PLoS1, (in review).

walkerJoshua Walker, Ph.D.

Uremic Solutes in a Vascular Model of Thrombosis

(December 2016 – present; Vipul Chitalia, MD, PhD)

Dr. Walker studies the effects of uremic toxicity among chronic kidney disease (CKD) patients as a possible cause of cardiovascular disease, in particular focusing on the role of indoxyl sulfate and kynurenine.  Indoxyl sulfate (IS) and kynurenine are uremic solute that are retained in the blood of CKD patients and potentially plays roles in the development of a pro-thrombic state among CKD patients.  The Chitalia lab has previously shown that IS enhances tissue factor (TF) expression through the aryl hydrocarbon pathway, which results in increased thrombosis.

Focusing on Kynurenine as a uremic solute in CKD patients as a prothrombotic mediator, we have begun to utilize vascular models of thrombosis, in vitro, using vascular smooth muscle cells (VSMCs).  Thus far, Dr. Walker has examined the effects of CKD and uremia on the expression of indoleamine-2-3-dioxygenase (IDO), the rate limiting enzyme that catabolizes tryptophan to kynurenine, which increases tissue factor expression through the aryl hydrocarbon pathway, leading to thrombosis.  Preliminary results suggest that kynurenine itself can increase IDO protein expression in a fast-forward loop, which could potentially result in an increased pro-thrombic state among CKD patients.  Future planned experiments in IDO knockout mice will confirm these findings in an animal model.  Additionally, Dr. Walker has begun experiments examining the effects of uremic solutes on regulation of lysl oxidase (LOX), a protein that the Ravid lab has previously been shown to regulate platelet reactivity and thrombosis.  Preliminary data by Dr. Walker shows that uremic solutes can upregulate LOX expression in VSMCs.  These results suggest a link between uremic solutes among CKD patients and increased thrombosis via LOX expression.


  1. Shashar, M. E. Belghasem, S. Matsuura, J. A. Walker, S. Richards, F. Alousi, K. Rijal, V. B. Kolachalama, M. Balcells, M. Odagi, K. Nagasawa, J. M. Henderson, A. Gautam, R. Rushmore, J. Francis, D. Kirchhofer, K. Kolandaivelu, D. H. Sherr, E. R. Edelman, K. Ravid, V. C. Chitalia. Targeting STUB1-Tissue Factor Axis Normalizes Hyperthrombotic Uremic Phenotype without Increasing Bleeding Risk. Science Translational Medicine, 2017, 9.

V.B. Kolachalama, M. Shashar, F. Alousi, S. Shivanna, K. Rijal, M. E., Belghasem, J. Walker, S.Matsuura, G. H. Chang, C. M. Gibson, L. M. Dember, J. M. Francis, K. Ravid, V. C. Chitalia. Uremic Solute-Aryl Hydrocarbon Receptor-Tissue Factor Axis Associates with Thrombosis after Vascular Injury in Humans.  Journal of the American Society of Nephrology, 2018(accepted January).

Oral Presentations:

“Global and Temporal Tissue-Specific Activation of AHR In Models of Discrete Models of Renal Disease”. American Society of Nephrology Kidney Week, October 2018, San Diego, CA.

Manuscript Submissions:

“Global and Temporal Tissue-Specific Activation of AHR In Models of Discrete Models of Renal Disease” Walker J, Richards S, Belghasem M, Arinze, N, Yoo S, Tashjian, J, Whelan S, Lee N, Kolochalama V, Francis J, Ravid K, Sherr D, Chitalia V, Kidney International, 2018. Under submission (Reviewed and received comments December 2018).

“Specific Tryptophan Metabolites Upregulated in a Mouse Model of Colon Cancer Induce Venous Thrombosis” Belghasem M, Roth D, Richards S, Walker J, Arinze N, Spencer C, Francis J, Thompson C, Andry C, Ravid K, Chitalia V, Blood, 2019, Under Submission.


Alessandra Fedoce Weaver, PhD

Glutaredoxin-1 overexpression May normalize hepatic lipid metabolism

(April, 2018 – present; Markus M. Bachschmid, PhD; mentor)

Non-alcoholic fatty liver (NAFL) disease is an emerging health problem prevalent in type-2 diabetes and obesity. The pathogenesis of NAFL (NAFLD) starts with asymptomatic lipid accumulation leading to liver inflammation and fibrosis. Glutaredoxin-1 (Glrx) ablated mice fed a chow diet develop NAFL and dyslipidemia. Paradoxically, Glrx ablation upregulated de novo lipogenesis in the liver. Lipid synthesis requires biological building blocks and redox equivalents including acetyl-CoA and NADPH. Glrx is an enzyme that removes GSH adducts of protein thiols, but its metabolic function remains unknown.


Poster presentation at the Gordon Research Conference on Oxidative Stress and Disease 2019, Ventura, CA.

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

Todd Sponholtz, PhD

Individual- and group-level clustering of cardiometabolic disease

(July 2018-present; Dr. Vasan S. Ramachandran; Mentor)

The metabolic syndrome (MetS) is defined by a set of set of cardiometabolic conditions (obesity, diabetes, hypertension, and dyslipidemia), that tend to co-occur within individuals. These conditions also tend to cluster geographically and within social networks. Dr. Sponholtz’s research explores the causes and consequences of this clustering. The ultimate goal of this research is to gain better understanding the relevant mechanisms and providing evidence to inform the design of interventions to prevent cardiometabolic and cardiovascular disease. Using data from the Framingham Heart Study, Dr. Sponholtz has focused on answering three main questions. First, how much of the variation in cardiovascular risk within populations is attributable to physical and social environments, and to what extent are people influenced by their environments versus being selected into similar social circles or environments? We are applying several statistical approaches, including multilevel modeling and stochastic actor-oriented models, in order to address this question. Second, the single nucleotide polymorphism (SNP) within the fat mass and obesity-associated (FTO) gene (rs9939609) is among the strongest genetic predictors of body mass index identified thus far. Prior research from the Framingham Heart Study reported that this association is stronger among participants born after 1942 than among those born before that year. We matched Framingham Heart Study participants to their parents’ examinations where the offspring was aged between 0 and 19 years, and investigated whether the associations of early life environmental exposures (using parents’ socioeconomic status and behavioral factors to proxy childhood environments) with adulthood BMI by rs9939609 genotype. Third, individuals may become obese without being metabolically unhealthy (defined as ≥2 of the component conditions, excluding obesity) or become metabolically unhealthy without obesity, with different implications for cardiovascular disease risk. Further, MetS-related measures (BMI, blood pressure, fasting blood glucose, serum triglycerides and HDL) can vary dynamically over time. We are investigating the potential interaction between obesity and metabolic health status in their relationships with cardiovascular disease, and the impact of long-term variability in MetS-related measures on cardiovascular health in a community-based population.


Published Manuscript:

Sponholtz TR, Vasan RS. Contribution of the neighborhood environment to cross-sectional variation in long-term CVD risk scores in the Framingham Heart Study. PLoS One. Aug 6; 13(8):e0201712

Submitted Manuscript:

Sponholtz TR, van den Heuvel ER, Xanthakis V, Vasan RS. Association of Variability in Obesity and Metabolic Health with Cardiometabolic Disease Risk. J Am Heart Assoc. 2018.

Manuscripts in Preparation:

Sponholtz TR, Xanthakis, V, Vasan RS. The Associations of Variability of Obesity and Metabolic Health with Subclinical Atherosclerosis. 2018.

Sponholtz TR, Liu Chunyu, Vasan RS. Associations of Early-Life Exposures with Adulthood Obesity in the Framingham Heart Study. 2018.

Sponholtz, TR, Bethea TN, Ruiz-Navarrez E, Palmer JR, Rosenberg L, Wise LA. Night shift work and fecundability in US Black Women. 2018.

Sponholtz, TR, et al. Risk Factors for Endometrial Cancer in African-American Women. 2018.

Educational Enrichment: None.

Conference Abstracts:

Sponholtz, TR, Vasan RS. Sex-Related Differences in the Association of Social Isolation with Plasma Leptin Concentration. Poster presentation accepted at the American Heart Association Epi/Lifestyle 2019 Scientific Sessions, March 5-8, 2019, Houston, TX.

Sponholtz, TR, Vasan RS. Sex-Related Differences in the Associations of Variability in Body Mass Index and Metabolic Health with Incidence of Obesity and Metabolically Unhealthy Status: The Framingham Offspring Study. Poster presentation accepted at the American Heart Association Epi/Lifestyle 2019 Scientific Sessions, March 5-8, 2019, Houston, TX.

Sponholtz, TR, Vasan RS. Childhood- and Adult Neighborhood-Level Variation in Adult Metabolic Syndrome Measures. Poster presentation accepted at the American Heart Association Epi/Lifestyle 2019 Scientific Sessions, March 5-8, 2019, Houston, TX.

Cristal Reyna Thompson

Characterization of hemostatic and thrombotic disorders of JAK2V617F mouse model of primary myelofibrosis

June 2018 – present;Mentor: Dr. Katya Ravid

Primary Myelofibrosis (PMF) is a chronic myeloproliferative neoplasm (MPN) characterized by excessive production of extracellular matrix (ECM) leading to fibrosis and megakaryocytosis in bone marrow. The most common mutation in PMF patients is the JAK2V617F hyperactivating mutation found in 50-60% of patients. Arterial and venous thrombosis are the leading causes of death and morbidity for MPN patients. Thrombosis has been correlated to the presence of the JAK2V617F mutation. It is thought that platelets bearing the JAK2V617F mutation play a critical role in thrombosis due to increased number and hyperreactivity. In collaboration with BU researchers, Dr. Thompson has found that transgenic mice expressing the human JAK2V617F gene in hematopoietic stem cells exhibiting PMF-like disease show an increase in bleeding time corresponding to hemostatic disorders known in MPN patients. In addition, platelets and megakaryocytes from these mice have increased adhesion to monomeric collagen and fibronectin. Interestingly, platelet aggregation with agonists ADP, monomeric collagen, fibrillar collagen, and thrombin was dampened compared to wild-type controls. Recent work conducted by Dr. Thompson has shown that JAK2V617F platelets have decreased ADP and ATP secretion compared to wild-type controls, pointing to a potential defect in platelet activation. Future work will focus on understanding the underlying mechanisms for both increased thrombosis and bleeding in mice carrying the JAK2V617F mutation with a focus on megakaryocyte and platelet function. This work will aid in implementing novel therapeutic methods for treating patients with MPN.

Meeting attendance:
Cell Biology of Megakaryocytes and Platelets, Galveston, TX, February 23-March 1