Speed Biosketch

OMB No. 0925-0001 and 0925-0002 (Rev. 10/2021 Approved Through 09/30/2024)

BIOGRAPHICAL SKETCH

EDUCATION/TRAINING 

Personal Statement

Throughout my predoctoral and postdoctoral career, my research revolved around the mechanisms by which renal and extrarenal endothelin-1 (ET-1) influences blood pressure. I was fortunate enough during my postdoctoral fellowship to have several animal models at my disposal including ETB receptor deficient rats and mouse models that allowed us to knockout out ETA receptors, ETB receptors and ET-1 in various tissues. Phenotyping these models led me to my current niche of studying the role of ET-1 in obesity and insulin resistance. They also provided me with the necessary research tools to start and lead an independent research program that began in January 2018 at the University of Mississippi Medical Center (UMMC).

Since joining UMMC, my research program has expanded dramatically, and mentoring has become a large part of my program. I have served on 8 thesis committees and trained 2 graduate students, 3 medical students, and 1 postdoctoral fellow. I am excited to serve as a mentor in the Cardiorenal and Metabolic Diseases Research Center, a role that aligns well with my goals as an academic researcher, one of which is to teach the next generation of scientists.

1. Rivera-Gonzalez OJ, Kasztan M, Johnston JG, Hyndman KA, Speed JS. Loss of endothelin type B receptor function improves insulin sensitivity in rats. Can J Physiol Pharmacol. 2020 Sep;98(9):604-610. PubMed Central PMCID: PMC7442597.
2. Jenkins HN, Williams LJ, Dungey A, Vick KD, Grayson BE, Speed JS. Elevated plasma endothelin-1 is associated with reduced weight loss post vertical sleeve gastrectomy. Surg Obes Relat Dis. 2019 Jul;15(7):1044-1050. PubMed Central PMCID: PMC6880647.
3. Speed JS, Hyndman KA, Roth K, Heimlich JB, Kasztan M, Fox BM, Johnston JG, Becker BK, Jin C, Gamble KL, Young ME, Pollock JS, Pollock DM. High dietary sodium causes dyssynchrony of the renal molecular clock in rats. Am J Physiol Renal Physiol. 2018 Jan 1;314(1):F89-F98. PubMed Central PMCID: PMC5866350.

Current Research Support

NIH/NIDDK- R01DK124327                           Speed (PI)                   4/1/2021-3/31/2026

$263,000/year direct funds

Endothelin-1 in Obesity and Insulin Resistance

The goal of this project is to determine mechanisms by which adipose tissue derived endothelin-1 promotes insulin resistance in obesity.

Completed Research Support

NIH/NHLBI-R00-HL127178                            Speed (PI)                       01/15/18-12/31/21

$249,000/year-No cost extension

Endothelin: Mechanisms in Hypertension and Obesity

The R00 phase will address the mechanisms by which ET-1 affects lipid metabolism by adipocytes and whether ET_A/ET_B receptor imbalance may contribute to the development of obesity.

NIH/NHLBI-R00-HL127178 Supplement       Speed (PI)                     1/1/2019-12/31/2021

$59,940/Year-No cost extension

This award is a minority supplement to R00 HL127178 in order to promote the career development of London Williams, a master’s student in my lab.

NIH/NIDDK- F3112917833                 Rivera-Gonzalez (PI)

Endothelin in Obesity Induced Insulin Resistance
This pre-doctoral fellowship aims to determine mechanisms by which ET-1 promotes insulin resistance in obese animals.
Role: Mentor

K99 HL127178-01A1, National Heart, Lung and Blood Institute (NHLBI)
Speed, Joshua S (PI)
01/15/16-12/31/17
Endothelin - Mechanisms in Hypertension and Obesity
For the K99 portion of this grant, the major goal is to determine the mechanisms by which extrarenal vascular endothelin-1 regulates skin Na+ storage during high salt intake. It will also address the mechanisms by which vascular ET-1 in upregulated in response to high salt intake. The R00 phase will address the mechanisms by which ET-1 affects lipid metabolism by adipocytes and whether receptor imbalance may contribute to the development of obesity.
Role: PI

15SDG25090194 , American Heart Association
Speed, Joshua S. (PI)
07/01/15-01/15/16
Extrarenal Control of Na+ Homeostasis and Blood Pressure by Endothelin-
The major goal of this grant is to determine the mechanisms by which extrarenal vascular endothelin-1 regulates skin Na+ storage during high salt intake. It will also address the mechanisms by which vascular ET-1 in upregulated in response to high salt intake.
Role: PI

12POST11800038, American Heart Association
Joshua Speed (PI)
07/01/12-06/30/14
Endothelin in Na+ Homeostasis and Hypertension

The major goal of this grant was to determine the mechanisms by which vascular ET-1 regulates Na+ handling by the skin.

Role: Post-Doctoral Scholar

09PRE2250470, American Heart Association

Speed, Joshua (PI)

07/01/09-06/30/11

The Kidney, Endothelin, and Hypertension
The major goal of this grant was to determine if a reduction in sodium excretion and elevation in arterial pressure during renal medullary ETB receptor blockade is due to a decrease in renal medullary production of 20-HETE and to determine if reduced renal ET-1 mediates elevated blood pressure in a model of salt sensitive hypertension.
Role: GR

Positions, Scientific Appointments and Honors

Positions and Scientific Appointments

Honors

Contribution to Science

1. During my predoctoral training, I gained an appreciation and deep knowledge of renal and cardiovascular physiology. My thesis was focused on how the renal inner medulla responded to high salt intake. Specifically, I studied the interaction between endothelin-1 and 20-HETE in the maintenance of salt homeostasis and blood pressure regulation. I found that an increase in renal medullary 20-HETE mediated the effects of endothelin-1 to inhibit sodium transport by the nephron. In addition, I determined that a reduction in renal medullary production of ET-1 was a part of the pathophysiology behind Dahl salt sensitive hypertensive rat
   1. Hall JE, Granger JP, do Carmo JM, da Silva AA, Dubinion J, George E, Hamza S, Speed J, Hall ME. Hypertension: physiology and pathophysiology. Compr Physiol. 2012 Oct;2(4):2393-442. PubMed PMID: 23720252
   2. Speed JS, George EM, Arany M, Cockrell K, Granger JP. Role of 20-hydroxyeicosatetraenoic acid in mediating hypertension in response to chronic renal medullary endothelin type B receptor blockade. PLoS One. 2011;6(10):e26063. PubMed Central PMCID: PMC3189228.
   3. Speed JS, LaMarca B, Berry H, Cockrell K, George EM, Granger JP. Renal medullary endothelin-1 is decreased in Dahl salt-sensitive rats. Am J Physiol Regul Integr Comp Physiol. 2011 Aug;301(2):R519-23. PubMed Central PMCID: PMC3154719.
   4. Granger JP, Abram S, Stec D, Chandler D, Speed JS, LaMarca B. Endothelin, the kidney, and hypertension. Curr Hypertens Rep. 2006 Aug;8(4):298-303. PubMed PMID: 16884660.
2. During my postdoctoral training, I continued researching the mechanisms of sodium homeostasis by the body to maintain extracellular fluid volume and blood pressure, particularly in response to high sodium intake. It was recently found that the ability of the skin to store sodium is an important buffer to maintain homeostasis. Typically, in response to an increase in salt intake, extracellular osmolality and sodium content are increased in the skin. We found that an increase in vascular endothelial derived endothelin-1, and subsequent activation of the ETA receptor, sequesters macrophages to the interstitium of the skin via an increase in cell adhesion molecules. The increase in macrophages has been shown to be imperative for the buffering mechanism of the skin to maintain sodium homeostasis.
   1. Speed JS, Hyndman KA, Kasztan M, Johnston JG, Roth KJ, Titze JM, Pollock DM. Diurnal pattern in skin Na⁺ and water content is associated with salt-sensitive hypertension in ET_B receptor-deficient rats. Am J Physiol Regul Integr Comp Physiol. 2018 Apr 1;314(4):R544-R551. PubMed Central PMCID: PMC5966816.
   2. Speed JS, Hyndman KA, Roth K, Heimlich JB, Kasztan M, Fox BM, Johnston JG, Becker BK, Jin C, Gamble KL, Young ME, Pollock JS, Pollock DM. High dietary sodium causes dyssynchrony of the renal molecular clock in rats. Am J Physiol Renal Physiol. 2018 Jan 1;314(1):F89-F98. PubMed Central PMCID: PMC5866350.
   3. Speed JS, Heimlich JB, Hyndman KA, Fox BM, Patel V, Yanagisawa M, Pollock JS, Titze JM, Pollock DM. Endothelin-1 as a master regulator of whole-body Na+ homeostasis. FASEB J. 2015 Dec;29(12):4937-44. PubMed Central PMCID: PMC4653060.
   4. Speed JS, Pollock DM. New clues towards solving the mystery of endothelin and blood pressure regulation. Hypertension. 2015 Aug;66(2):275-7. PubMed Central PMCID: PMC4498997.
3. As I transitioned from a postdoctoral fellow into an independent researcher, I became interested in the role of endothelin-1 in the pathophysiology of metabolic syndrome, specifically in relation to insulin resistance in obesity. Endothelin-1 is elevated in obese populations and is associated with insulin resistance. We have ample preliminary data to suggest that Endothelin Type B receptor (ETB) activation promotes insulin resistance and may modulate changes in adiposity. Our lab has recently published that plasma ET-1 levels are inversely related to body weight loss following vertical sleeve gastrectomy. We have also published several abstracts showing that whole body loss of ETB receptor function improves fasting glucose, glucose tolerance, and insulin tolerance in rodents. Therefore, the goal of the lab is to elucidate mechanisms by which ET-1 promotes insulin resistance.
   1. Rivera-Gonzalez O, Wilson NA, Coats LE, Taylor EB, Speed JS. Endothelin receptor antagonism improves glucose handling, dyslipidemia, and adipose tissue inflammation in obese mice. Clin Sci (Lond). 2021 Jul 30;135(14):1773-1789. PubMed PMID: 34278410.
   2. Speed JS, Pruett WA, Lirette ST, Cook JJ, Phillips CL, Grayson BE. Cardiovascular Risk Factors Following Vertical Sleeve Gastrectomy in Black Americans Compared with White Americans. Obes Surg. 2021 Mar;31(3):1004-1012. PubMed Central PMCID: PMC7897752.
   3. Jenkins HN, Rivera-Gonzalez O, Gibert Y, Speed JS. Endothelin-1 in the pathophysiology of obesity and insulin resistance. Obes Rev. 2020 Dec;21(12):e13086. PubMed Central PMCID: PMC7669671.
   4. Jenkins HN, Williams LJ, Dungey A, Vick KD, Grayson BE, Speed JS. Elevated plasma endothelin-1 is associated with reduced weight loss post vertical sleeve gastrectomy. Surg Obes Relat Dis. 2019 Jul;15(7):1044-1050. PubMed Central PMCID: PMC6880647