Research Focus: Part Four

March 9, 2013 by Leave a Comment

Over a medical research career that spans more than two decades, Stephen M. Black has conducted considerable research on a variety of topics. He currently has six ongoing research projects he is working on with his integrated cardiovascular laboratory at Georgia Regents University.

One of the research projects discussed in Stephen M. Black’s most recent blog post, “Endothelial barrier protection and repair in acute lung injury”, is a Program Project, meaning that the Regents Professor is working with one or more of his colleagues at Georgia Regents University to complete the project. The project is comprised of four interrelated projects and three cores, which all use state-of-the-art biochemical, cellular, molecular, and physiological approaches. Stephen M. Black hopes that the Program Project will provide the medical community with a better understanding of the mechanisms by which RhoA (a small GTPase protein) and Rac1 (a protein found in human cells) are regulated during G- and G+-induced acute lung injury. This data should also help in the development of new strategies and treatments for acute lung injury, which has not seen a major drop in fatalities in over 40 years (learn more on acute lung injury here).

The study’s four inter-related projects are:

Project 1: This project focuses on how protein nitration regulates RhoA and Rac1 signaling during the development of acute lung injury, and makes use of biochemical, cellular, molecular, and animal studies.
Project 2: This project is thematically linked to Project 1, as it deals with determining how heat shock protein 90 (Hsp90) impacts RhoA activation and downstream Rac1 signaling.
Project 3: The third project also focuses on RhoA and Rac1, aiming to determine the therapeutic potential of monitoring their expression both in a living organism (in vitro) and in a test tube environment (in vivo).
Project 4: This project investigates the barrier disruptive effects of the G+ pore forming toxins, lysteriolysin and pneumolysin. The results should reveal the mechanisms of RhoA/Rac1 imbalance while exploring the therapeutic potential of enhanced NO signaling for restoring this balance during G+ mediated acute lung injury.

Learn more about Stephen M. Black and his research by connecting with him on Zerply or by reading his blog posts on WordPress: http://stephenmblack.wordpress.com/

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Research Focus: Part Three

February 25, 2013 by 1 Comment

Stephen M. Black and his integrated cardiovascular laboratory are focused on a number of research projects that intend to expand our knowledge of conditions such as congenital heart disease and pulmonary hypertension. Last week’s blog post focused on two such research projects: Role of altered carnitine metabolism in perinatal endothelial dysfunction and ROS in pulmonary hypertension: role of ADMA. Two more ongoing research projects that have not been discussed on this blog are:

 

Role of neural NOS in neurotoxicity

Recent data collected in Stephen M. Black’s laboratory indicates that a developing brain is more vulnerable to hypoxia-ischemia (HI) injury than the mature brain due to a deficiency in anti-oxidant enzyme capacity. The severe form of an HI injury is responsible for blindness, epilepsy, mental retardation, and cerebral palsy, so Stephen M. Black recognizes the importance of finding an HI therapy for developing brains. His recent data shows that an increase in reactive oxygen species (ROS) generation in the presence of nitric oxide synthase (NOS) leads to an increase in HI. The study hypothesizes that hydroxyl radical, generated following activation of NOS and an increase in NO, is the key mediator of neural loss after HI. Stephen M. Black hopes that the results will help identify signaling agents that can be targeted for treating individuals exposed to asphxia.

Endothelial barrier protection and repair in acute lung injury

This Program Project (a medical research project involving more than one of an institution’s medical researchers) is focused on defining the role of vascular endothelial cell (EC) permeability as a component in acute lung injury (ALI). A team of productive experts are focusing on four interrelated projects and 3 cores with the hope that the participating researchers’ state-of-the-art cellular, molecular, biochemical, and physiological approaches will lead to a better understanding of how RhoA and Rac1 are regulated during G- and G+-induced ALI. A future blog post will explain how each project and core will help researchers meet this goal.

Stephen M. Black is focused on these and many other medical research projects. Learn more about his medical research by visiting his Bigsight profile: http://bigsight.org/stephen_m_black

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Research Focus: Part 2

February 16, 2013 by 1 Comment

Last week’s blog post took a look at two areas that Stephen M. Black is currently researching: Perinatal regulation of endothelial NOS, and Perinatal regulation of TGF-beta1 during vascular remodeling. However, there are many more research projects on which Stephen M. Black and his integrated cardiovascular laboratory are focusing. Most of his research, which extramurally funded by outside parties, is intended to help the medical community gain a better understanding of how reactive nitrogen species (RNS) generations alters function both in a living organism (in vitro) and in a test tube environment (in vivo). Ongoing research projects that have not previously been discussed are:

 

Role of altered carnitine metabolism in perinatal endothelial dysfunction

Based on Stephen M. Black’s recent study involving a lamb model of congenital heart disease and increased pulmonary blood flow, the development of endothelial dysfunction has been shown to be associated with derangements (disruptions) in nitric oxide (NO) signaling. Since the mechanisms by which endothelial dysfunction occurs have not been adequately resolved, this study aims to do two things: reveal the mechanisms that underlie disruption of carnitine metabolism in the previously mentioned lamb model, and utilize L-carnitine (a compound used for decades to treat inborn metabolism errors) as a therapeutic agent for the endothelial dysfunction associated with congenital heart disease. The study’s results should provide the medical community with a better understanding of the role mitochondrial dysfunction plays in congenital heart disease and determine if L-carnitine is an effective treatment strategy.

ROS in pulmonary hypertension: role of ADMA

In previous studies involving a lamb model, Stephen M. Black has shown that increased reactive oxygen species (ROS) generation in the pulmonary vessels influences the development of pulmonary hypertension. New preliminary data shows that increased ROS generation also correlates with an elevation in asymmetric dimethyl arginine (ADMA) levels and a decrease in tetrahydrobiopterin (BH4) levels. This study should elucidate the medical commuity’s understanding of the role ADMA plays in the mitochondrial dysfunction process, and how diminied NO-signaling and endothelial dysfunction trigger pulmonary hypertension secondary to increased pulmonary blood flow. This study could also suggest new signaling pathways that improve treatment of infants and children with pulmonary hypertension.

These are just two of the many active research projects on which Stephen M. Black is focused. Learn more about his research by reading some of the questions he has answered on his Quora.

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Research Focus

February 7, 2013 by 1 Comment

Stephen M. Black is a Regents Professor with Georgia Regents University’s Department of Obstetrics and Gynecology (learn more). Over the course of his career, Stephen M. Black has been published in over 150 medical journal articles featuring his findings from dozens of medical research projects. Currently Stephen M. Black and his integrated cardiovascular laboratory have several research projects that are extramurally funded (funded by outside parties) or pending funding. His focus has been on understanding how reactive nitrogen species (RNS) generation alters function both in vitro (in a living organism) and in vivo (in a test tube environment). Below are some of the subjects that Stephen M. Black is currently researching:

 

Perinatal regulation of endothelial NOS

This study aims to understand how endothelial nitrous oxide synthase (eNOS) signaling is regulated in the pulmonary system during the perinatal stage. Stephen M. Black hopes that gaining an understanding of how ET-1 interactions mediate changes in a child’s pulmonary blood flow (PBF) following surgery might improve peri-operative treatment strategies to reduce short and long-term morbidity and mortality among children with congenital heart defects (CHD).

Perinatal regulation of TGF-beta1 during vascular remodeling

Abnormal structural development of the pulmonary circulation continues to lead to morbidity and late mortality for children born with CHD. Stephen M. Black hopes that this project will test the hypotheses that increased pulmonary circulation is due, at least in part, to a shear stress dependent increase in vascular endothelial growth factor (VEGF) expression mediated by increased activation of transforming growth factor-beta 1 (TGF-beta1), as well as that nitrous oxide (NO) plays a key role in the previously mentioned process.  The resulting research will shed a light on which biomedical forces regulate the TGF-beta1/VEGF axis, which will help medical professionals such as Stephen M. Black develop new treatment strategies for children born with CHD.

 

These are just two of the active research projects on which Stephen M. Black is focused. Learn more about his research by connecting with Stephen M. Black on Quora.

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