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do Carmo Biosketch

OMB No. 0925-0001 and 0925-0002 (Rev. 10/2021 Approved Through 01/31/2026)

BIOGRAPHICAL SKETCH

NAME: Jussara Marcia do Carmo
eRA COMMONS USER NAME (credential, e.g., agency login): JDOCARMO
POSITION TITLE: Associate Professor
EDUCATION/TRAINING 

INSTITUTION AND LOCATION

DEGREE

(if applicable)

 

Completion Date

MM/YYYY

 

FIELD OF STUDY

 

State University of Paraiba, Brazil

BS

12/1993

Physical Therapy

Federal University of Pernambuco, Brazil

M.S.

05/1999

Physiology

University of Sao Paulo

Ph.D.

10/2006

Physiology

Univ. Mississippi Medical Center, Jackson, MS

Postdoctoral Fellow

06/2008

Physiology

Personal Statement

The focus of my research has been to understand the mechanisms of renal injury and hypertension that develop in offspring from obese parents. Specifically, we are investigating renal mechanisms by which developmental programming caused by parental obesity and its metabolic abnormalities lead to activation of P2X purinoceptor 7 (P2X7R) and amplification of kidney injury in the offspring, and how therapeutic interventions may improve the long-term health of the offspring from obese parents. Therefore, a new focus of our team has been to unravel the mechanisms of parental obesity-induced developmental programming of renal dysfunction. Our laboratory has also focused on unravelling the central nervous system (CNS) signaling mechanisms and brain regions involved in the regulation of metabolic and cardiovascular function by the leptin-melanocortin axis. Additionally, we are investigating the powerful beneficial effects of the leptin-melanocortin axis on cardiac function in models of myocardial infarction and ischemia/reperfusion injury. We have generated novel genetic mouse models that allow us to unravel the role of the leptin-melanocortin pathway in specific brain nuclei which accompanied by our expertise in conducting acute and chronic sophisticated and integrative physiological studies in mice provide unique and powerful approach to determine the complex circuits and signaling pathways of the CNS control of appetite, BP regulation, cardiac and metabolic functions with broad implication for clinical treatment of cardiovascular and metabolic diseases. Scientific progress is accelerated and enhanced by diverse scientists and trainees interacting and challenging each other at all levels. As a scientist, I am deeply committed to scientific rigor, training, mentoring, promoting diverse, inclusive, safe and supportive scientific environments.
Ongoing and recently completed projects include:
Active

NIH/NHLBI 1R01HL163076        do Carmo (MPI with Dr. Da Silva)      01/09/2023-12/31/2026                3.0
“Cardiac protective mechanisms of melanocortin system activation”
The major goal of this project is to examine the mechanisms by which activation of brain melanocortin 4 receptors protects the heart against progressive heart failure in myocardial infarction.
Role: PI
No overlap

RO1 DK121411             (JM do Carmo, PI)             09/19/19 - 07/31/2023                                             3.6
NIH/NIDDK “Long-term consequences of parental obesity on developmental programming of cardiorenal diseases in offspring”
Role: PI
No overlap

NI P20 GM 104357         (JE Hall, PI)                     09/05/2013-04/30/2023                                            0.8
National Institutes of Health, National Institute of General Medical Science
Cardiorenal and Metabolic Diseases Research Center
The long-term goal is to develop the Cardiorenal and Metabolic Disease Research Center and provide infrastructure for multidisciplinary, diverse group of basic, clinical and population scientists working on the common synergistic theme of obesity, cardiorenal and metabolic diseases and to facilitate their collaborations.
Role: Sub-Core Director, Basic Science – Metabolic Phenotyping

NI P20 GM 104357-Supplement        (JE Hall, PI)           07/01/2021-04/30/2023                                    2.4
National Institutes of Health, National Institute of General Medical Science
Cardiorenal and Metabolic Diseases Research Center
The goal of this supplement grant is to generate preliminary data for R01 application aiming at investigating the consequences of parental obesity on offspring cognitive dysfunction and cardiometabolic dysfunction, and potential mechanisms involved.
Role: Supplement Project PI
No overlap

Previous

P20 RR024217     do Carmo (PI of Project II)               09/05/2013-04/30/2018                         $175,000/year
NIH/NHLBI 
"Hypertension and Cardiorenal Diseases Research Center"
The major long-term goal of this project is to investigate the effects of ambient temperature in modulating the actions of leptin on appetite, metabolic and cardiovascular function.
Role: PI of Project II

Positions, Scientific Appointments, and Honors

Professional Experience/Post Graduate Training

1993-1996       Assistant Professor, State University of Paraiba, Campina Grande, State of Paraiba, Brazil.

1996-2002       Assistant Professor, University of Tiradentes, Aracaju, State of Sergipe, Brazil.

1996-1999       Graduate Student, Master in Physiology, Federal University of Pernambuco, State of Pernambuco, Brazil.

2002-2006       Graduate Student – Doctorate in Physiology, University of Sao Paulo, State of Sao Paulo, Brazil.

2006-2008       Postdoctoral Fellowship, University of Mississippi Medical Center, Dept.  Physiology, Jackson, Mississippi, USA

2009-2010       Instructor, University of Mississippi Medical Center, Dept. Physiology, Jackson, Mississippi, USA.

2011-2018       Assistant Professor, University of Mississippi Medical Center, Dept. Physiology, Jackson, Mississippi.

2012-present Fellow, American Heart Association.

2018-present Associate Professor, University of Mississippi Medical Center, Dept. Physiology, Jackson, Mississippi.

Other Experience and Professional Memberships

1995-present – Brazilian Physiology and Therapeutics Society

2006-present – American Physiological Society

2006-present – American Heart Association

2012-present – Fellow, American Heart Association

Fellowships, Awards, Honors

1993-1996   Scholarship recipient, Pre-Doc, Coordination of the Improvement of Higher Education Personnel (CAPES),  Research Foundation, Brazil

2002-2006    Doctoral fellowship grant from Coordination of the Improvement of Higher Education Personnel (CAPES), Research Foundation, Brazil

2003             Travel Award from Foundation of Support to Teaching and Research (FAEPA), University of Sao Paulo, Brazil

2004             Travel Award from Office of Dean for Doctoral  Program  (Pro-Reitoria), University of Sao Paulo

2007             Young Investigator Travel Award, Council for High Blood Pressure    Research, Tucson, AZ

2011             American Physiological Society (APS)/NIDDK Minority Travel Fellowship Award,
                     Experimental Biology, Washington, DC.

2011-2014   Scientist Development Grant – American Heart Association (AHA)

2011             Finalist, Harry Goldblatt Award for New Investigators
                    American Heart Association, Council for High Blood Pressure Research

2012            Recipient, Harry Goldblatt Award for New Investigators
                    American Heart Association, Council for High Blood Pressure Research

2013            Young Investigator Award, American Heart Association
                    Council for High Blood Pressure Research in Australia. Melbourne, Australia

2013            Excellence in Research Award – University of Mississippi Medical Center  – Silver  Medallion

2014            NISBRE Highlighted Poster, Mississippi IDeA Network of Biomedical Research Excellence
                   (INBRE) Conference, Biloxi, MS - Cardiovascular Section

2016           Excellence in Research Award – University of Mississippi Medical Center – Gold Medallion

2017           Distinction in Scholarship; Selection for APS Select, TheAmerican Journal of Physiology –
                   Endocrinology and Metabolism, article title: "Role of autonomic nervous system in chronic CNS-
                   mediated antidiabetic action of leptin" APS Select            

2021           Distinction in Scholarship; Selection for APS Select, TheAmerican Journal of Physiology – Heart and
                   Circulatory Physiology, article title: "Sex differences in the impact of parental obesity on offspring
                   cardiac SIRT3 expression, mitochondrial efficiency and diastolic function early in life" APS Select

Contributions to Science (Selected from over 70 publications)
My research has focused on understanding the renal mechanisms that contribute to altered blood pressure control during obesity and developmental programming of cardiorenal diseases in offspring born from obese parents.

  1. The leptin-melanocortin system plays a crucial role in regulating appetite, energy expenditure and sympathetic nervous system (SNS) activity. This is evident by the fact that mutation of ob (leptin) gene or melanocortin-4 receptors (MC4R) result in severe obese phenotype in mice and human due to increased food intake and reduced energy expenditure but they have normal or slightly reduced blood pressure. Besides its effect on body weight regulation and SNS activity, leptin-melanocortin system also regulates peripheral glucose uptake. The past few decades have witnessed an unprecedented increase in the incidence of cardiovascular, renal and metabolic diseases such as diabetes. Of the people diagnosed with diabetes, about 80 to 90 percent are diagnosed as obese suggesting the close link between diabetes and obesity. My early paper examined the role of leptin on glucose regulation and baroreflex sensitivity in streptozotocin (STZ) - induced diabetes. We showed that central nervous system actions of leptin abolished the hyperglycemia and altered baroreflex sensitivity and intrinsic heart rate in this model of diabetes. We also showed that leptin receptor in proopiomelanocortin neurons is necessary for the chronic effects of leptin to raise blood pressure and reduce glucose levels. Recently we demonstrated that the brain leptin-melanocortin axis also exert remarkable effects that protect the heart against progressive cardiac dysfunction and heart failure after myocardial infarction (MI). However, many questions still unanswered, for instance, the central nervous system mechanisms triggered by chronic leptin infusion that mediates increased peripheral glucose uptake and improve cardiac function after MI is still unknown and it is one of the focus of our research effort.
    1.  Gava FN, da Silva AA, Dai X, Harmancey R, Ashraf S, Omoto ACM, Salgado MC, Moak SP, Li X, Hall JE, do Carmo JM. Restoration of cardiac function after myocardial infarction by long-term activation of the CNS leptin-melanocortin system. JACC: Basic Transl Sci. 2021; 6: 55-70
    2. da Silva AA, Spradley FT, Granger JP, Hall JE, do Carmo JM. Brain-mediated antidiabetic, anorexic, and cardiovascular actions of leptin require melanocortin-4 receptor signaling. J Neurophysiol 113: 2786-91, 2015. PMID: 25717164.
    3. do Carmo JM, da Silva AA, Cai Z, Lin S, Dubinion JH, Hall JE. Control of blood pressure, appetite, and glucose by leptin in mice lacking leptin receptors in proopiomelanocortin neurons. Hypertension. 57: 918-926. 2011. PMID: 21422382
    4. da Silva AA, do Carmo JM, Freeman JN, Tallam LS, Hall JE. A functional melanocortin system is required for CNS-mediated antidiabetic and cardiovascular actions of leptin. Diabetes. 58: 1749-1756, 2009. PMID: 19491210
    5. do Carmo JM, Hall JE, da Silva AA. Chronic central leptin infusion restores cardiac sympathetic-vagal balance and baroreflex activity in diabetic rats. Am J Physiol Heart Circ Physiol. 295: H1974-81, 2008. PMID: 18790839
    6. da Silva AA, do Carmo JM, Wang Z, Hall JE. The brain melanocortin system, sympathetic control and obesity hypertension. Physiology (Bethesda) 29:196-202, 2014.
    7. da Silva AA, do Carmo JM, Hall JE. CNS Regulation of Glucose Homeostasis: Role of the Leptin-Melanocortin System. Curr Diab Rep 20(7):29, 2020. PMID: 32451760.
  2. In addition to the studies described above, we have also examined the role of the brain leptin-melanocortin system in linking obesity with increased sympathetic activity and hypertension. These studies emphasized which specific brain regions are most important in mediating the effects of leptin-melanocortin-4 receptor activation on food intake, energy expenditure and blood pressure regulation. This body of work provides fundamental insights into metabolic and cardiovascular regulation that may lead to therapeutic approaches to improve body weight control and metabolic functions independent of increased blood pressure.  
    1. do Carmo JM, da Silva AA, Hall JE. Role of hindbrain melanocortin-4 receptor activity in controlling cardiovascular and metabolic functions in spontaneously hypertensive rats. J Physiol Hypertens 33: 1201-6, 2015. PMID: 25668357
    2. do Carmo JM, da Silva AA, Dubinion J, Sessums PO, Ebaady SH, Wang Z, Hall JE. Control of metabolic and cardiovascular function by the leptin-brain melanocortin pathway. IUBMB Life 65(8):692-8, 2013.
    3. do Carmo JM, da Silva AA, Rushing JS, Pace B, Hall JE. Differential control of appetite and cardiovascular function in mice with selective rescue of melanocortin-4 receptor in proopiomelanocortin neurons. Am J Physiol Regul Integr Comp Physiol 305(4):R359-68, 2013.
    4. do Carmo JM, Bassi M, da Silva AA, Hall JE. Systemic but not central nervous system nitric oxide synthase inhibition exacerbates the hypertensive effects of chronic melanocortin-3/4 receptor activation. Hypertension. 57: 428-34, 2011. PMID: 21263126
    5. do Carmo JM, da Silva AA, Rushing JS, Hall JE. Activation of the central melanocortin system contributes to the increased arterial pressure in obese Zucker rats. Am J Physiol Regul Integr Comp Physiol 302(5):R561-R567, 2012. PMID: 22204957
      f. do Carmo JM, Tallam SM, Roberts JV, Brandon EL, Biglane J, Silva AA Hall JE. Impact of obesity on renal structure and function in the presence and absence of hypertension: evidence from melanocortin 4 receptor deficient mice. Am J Physiol Regul Integr Comp Physiol. 297: R803:R812, 2009. PMID: 19605765.
  2.  
  3. The complex central nervous system (CNS) circuits and cell signaling mechanisms for the differential control of leptin’s metabolic and cardiovascular effects remain poorly understood. We are using novel genetically engineered mouse models and sophisticated state-of-the-art molecular and integrative physiological phenotyping to study the role of leptin receptor signaling via downstream signaling in specific areas of the CNS in mediating its chronic metabolic and cardiovascular effects. The outcome from our experiments will provide important and novel information that could lead to new therapeutic approaches for the treatment of hypertension and metabolic disorders, including obesity and diabetes, which are major causes of cardiovascular and renal disease worldwide.
  4.  
  5. a. da Silva AA, Freeman JN, Hall JE, do Carmo JM. Control of Appetite, Blood Glucose ad Blood Pressure           During Melanocortin-4 Activation in Normoglycemic and Diabetic NPY Deficient Mice. Am J Physiol                 Integr Comp Physiol. 314: R533-R539, 2017PMID: 29351428
  6. b.  do Carmo JM, da Silva AA, Freeman JN, Wang Z, Moak SP, Hankins MW, Drummond HA, Hall JE.  Neuronal Suppressor of Cytokine Signaling 3: Role in Modulating Chronic Metabolic and Cardiovascular Effects of Leptin. Hypertension Hypertension. 71: 1248-1257, 2018. PMID: 29686012
  7. c.  do Carmo JM, da Silva AA, Ebaady SE, Sessums PO, Abraham RS, Elmquist JK, Lowell BB, Hall JE. Shp2 signaling in Pomc neurons is important for leptin’s actions on blood pressure, energy balance and glucose regulation. Am J Physiol Regul Integr Com Physiol 307: R1438-47, 2014. PMID: 25339680
  8. d. da Silva AA, do Carmo JM, Wang Z, Hall JE. The brain melanocortin system, sympathetic control and obesity hypertension. Physiology (Bethesda) 29:196-202, 2014.
  9. e. do Carmo JM, da Silva AA, Gava FN, Moak SP, Dai X, Hall JE. Impact of leptin deficiency compared with neuronal-specific leptin receptor deletion on cardiometabolic regulation. Am J Physiol Regul Integr Comp Physiol 317(4):R552-62, 2019. PMID: 31411897
  10. f. Wang Z, do Carmo JM, Aberdein N, Zhou X, Williams JM, da Silva AA, Hall JE. Synergistic interaction of hypertension and diabetes in promoting kidney injury and the role of endoplasmic reticulum stress. Hypertension. 2017; 69: 879-891. PMID: 28348018
The model of parental obesity in rodents results in metabolic abnormalities, and increased blood pressure and cardiovascular responses to stress in male, but not in aged-matched female mice. There is limited understanding of the mechanisms by which parental obesity increases susceptibility of their offspring to cardiometabolic diseases, especially kidney and cardiac dysfunction. The impact of parental obesity on male offspring blood pressure regulation is markedly attenuated on the offspring of obese purinergic receptor 7 (P2X7R)-KO parents. My current research focus involves not only the mechanisms that contribute to the etiology of renal dysfunction that develops in response to developmental programming induced by obesity, but also explores the deleterious effects on cardiac function and inflammation in a sex-dependent manner in offspring from obese parents. Thus, more recent studies in my laboratory focus on sex differences in the impact of parental obesity on offspring cardiac sirtuin 3 expression, mitochondrial efficiency and diastolic function early in life.
  1. da Silva AA, Moak SP, Dai X, Borges GC, Omoto ACM, Wang Z, Li X, Mouton A, Hall JE, do Carmo JM. Parental obesity alters offspring blood pressure regulation and cardiovascular responses to stress: role of P2X7R and sex differences. Am J Reg Integr. In Press (MS# R-00300-2021)
  2. do Carmo JM, Omoto AC, Dai X, Moak SP, Li X, Wang Z, Mouton A, Hall JE, da Silva AA. Sex differences in the impact of parental obesity on offspring cardiac SIRT3 expression, mitochondrial efficiency and diastolic function early in life. Am J Physiol Heart Circ Physiol. 2021; 321: H485-H495. PMCID: 34296964
  3. Hall JE, Mouton AJ, da Silva AA, Omoto ACM, Wang Z, Li X, do Carmo JM. Obesity, kidney dysfunction, and inflammation: interactions in hypertension. Cardiovasc Res. 2021; 117: 1859-1876. PMCID: PMC8262632
  4. da Silva AA, Pinkerton MA, Spradley FT, Palei AC, Hall JE, do Carmo JM. Chronic CNS-mediated cardiometabolic actions of leptin: potential role of sex differences. Am J Physiol Regul Integ Comp Physiol. 2021; 320: R173-81. PMCID: 33206555

Published Work Listed in MyBibliography:

https://www.ncbi.nlm.nih.gov/myncbi/1x7imfM1imy5D/bibliography/public/

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