Stem Cell Expert Simmons to Lead Research Program
At Brown Foundation Institute of Molecular Medicine
HOUSTON – (May 18, 2006)–An international authority on adult blood stem cells and other bone-marrow stem cells, Paul J. Simmons, Ph.D., will lead a new research effort at The University of Texas Health Science Center at Houston.
Dr. Paul Simmons (far right) inspects what will soon be his new lab space at the IMM's Sarofim Research Building, with current UT-Houston Development Board President David Grimes & wife Windi (left), accompanied by Suzie & Phil Conway, past-president of the Development Board. (PHOTO by Bruce Bennett)
“We are thrilled to recruit Dr. Paul Simmons as the leader of the Center for Stem Cell Biology at the Brown Foundation Institute of Molecular Medicine for the Prevention of Human Disease (IMM). He is an outstanding stem cell scientist, and his recruitment will elevate our stem cell program to a new level,” UT Health Science Center President James T. Willerson, M.D., said.
Simmons is program head in Stem Cell Research at the Peter MacCallum Cancer Institute in Melbourne, Australia. His research team at “the PeterMac” focuses on the fine molecular details of blood stem cells and of mesenchymal stem cells, which differentiate into bone, cartilage and fat tissue and are thought to have potential for repairing other types of tissue as well. He also is president-elect of the International Society for Stem Cell Research.
“I am delighted that Dr. Simmons will be joining the IMM to direct our Stem Cell Research Center. He will help us recruit additional outstanding scientists to expand our current research effort in stem cell biology,” said IMM Director Ferid Murad, M.D., Ph.D., 1998 Nobel Laureate in Physiology or Medicine. “This is an exciting time to apply this technology to many important and devastating diseases. He will bring some fresh and important approaches to the Institute with regard to stem cell research.”
Simmons is expected to recruit another dozen scientists to the IMM, an effort bolstered by the recently completed $230-million New Frontiers fundraising campaign.
“We have a responsibility to drive stem cell research from bench to bedside on a foundation of excellence in basic research.” Simmons said. “This is a new discipline at the juncture of stem cell biology, bioengineering and nanotechnology. New discoveries come at the interface between different disciplines and institutions. The opportunities here in Houston are absolutely outstanding. Who wouldn’t jump at the chance to run a large new stem cell program in the largest medical center in the world?”
Simmons’ work is pushing the boundaries of stem cell research in important ways, said the IMM’s COO, Director- and CEO-Elect C. Thomas Caskey, M.D. “Dr. Simmons’ success in the study of blood-derived stem cells created the platform which launched research to determine how stem cells are differentiated into red cells, white cells, platelets, muscle, or neural cells. Deciphering this important question will lead to unprecedented safe therapeutic solutions.”
Adult stem cells are specialized cells designed to renew the body’s tissues. Although every adult organ probably has its own resident population of stem cells, such cells have only been identified and their properties defined in a limited range of organs. Stem cells in adult tissues also comprise only a very minor population of the total cells.
To develop effective cellular therapies for the treatment of diseases, there is a need not only to isolate the rare stem cells from the organ to be treated but also to establish technologies to increase the numbers of stem cells available for the therapy. Simmons has a strong record of both identifying stem cells and in developing culture conditions to propagate adult stem cells to generate the large numbers of cells needed for therapeutic applications.
Simmons’ research focuses on improving existing treatments with blood stem cells, understanding the molecular details of blood and mesenchymal stem cells and their environments in the body, and using techniques honed in these two areas to branch out into the study of more poorly understood stem cells in other adult tissues, including the lungs and kidneys.
“It’s important to understand stem cell niches – the key environment and growth factors that support self-renewal of stem cells in the body,” Simmons said. “You understand the cellular and molecular components of the niche so you can replicate the niche’s function out of the body to improve your ability to grow stem cells for therapeutic use.”
Blood stem cells, also called hematopoietic stem cells, originate in the bone marrow and differentiate into red cells, white cells, platelets – all the cells required for blood. It is these cells that are given intravenously to restore the blood supply of patients who have been treated for diseases such as leukemia in the misnamed procedure commonly known as a bone marrow transplant.
Simmons’ is looking at ways of making blood stem cell transplants safer. Patients face a period of about eight days after transplantation when no new mature blood cells are generated, including the infection-fighting white cells. Patients are extremely vulnerable to infection at this time, and can die from infectious complications.
Simmons’ group developed a means to include more leukocyte-making progenitor cells in transplants. “The clinical trial in this regard was a complete success,” Simmons said, infection-fighting cells were boosted and there were no episodes of infection.
However, the team had also hoped to also see a greater return of the production of platelets which promote blood clotting, but this did not occur.
“This highlights the great importance of getting involved in clinical trials,” Simmons said. “The first part was successful, the second part was not. So you go back to the bench (the laboratory) with a clear understanding of where improvements are required, design experiments to identify the problem and to test solutions and then come back to the clinic to test the improved protocol. It’s a reiterative loop that focuses and streamlines translational research with the intention to optimize clinical outcomes for the patient.”
In the case of mesenchymal stem cells, also produced in the bone marrow, Simmons developed an antibody that served as a biomarker to identify these cells, a breakthrough finding. In a landmark paper three years ago, Simmons’ team reported isolating and purifying a population of mesenchymal stem cells and described their ability to differentiate into bone, cartilage and fat.
The rare mesenchymal stem cells are found at a ratio of about 1 cell in 10,000 bone marrow cells, but Simmons’ team cultured a population in which one in two cells grows into a mesenchymal stem cell. These accomplishments are being replicated in a mouse model, where transgenic and knockout models will be used to ask fundamental questions about these cells.
His research will continue to pursue the details of blood and mesenchymal stem cells, including a look at their application in cardiovascular and skeletal diseases.
Simmons plans to apply his methods of identifying, growing and studying adult stem cells in other tissues, in particular the lungs and kidneys.
“There is a paucity of effective treatment for cystic fibrosis, chronic obstructive pulmonary disease, and other lung diseases,” Simmons said. “There’s little understanding of the stem cells in the respiratory system. We need to characterize them in order to study their properties and to identify regulators of their growth and differentiation. This will provide important clues as to how to derive lung precursors from stem cells and will ultimately enable the development of novel cellular therapies for the treatment of currently intractable lung diseases.”
Another huge area of unmet medical need is kidney disease. “We face a tsunami of kidney disease on the horizon, driven in part by the marked increase in diabetes,” he said. “Short of kidney transplantation, current treatments for renal failure are a ‘band aid.’ More effective therapies will be required. We will seek renal stem cells. It’s a very challenging area but the sooner we get there the better.”
Following a May 16 ribbon-cutting ceremony, the IMM will move into a state-of-the-art new home, the $120 million Fayez S. Sarofim Research Building at 1825 Pressler St. in the Texas Medical Center.
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