Joerg R. Leheste, Ph.D., stares into fish tanks ... contemplating, marveling. The score or so of clear plastic rectangular boxes connected by tubes are key to his research and the answer to the question that enthralls him: Can the blind be made to see again?
Inside their tanks, unaware of the faith Leheste has placed in them, swim hundreds of zebrafish. Striped, freshwater fish the size of a pinky: These unlikely heroes may hold the key to understanding and reversing many human ailments. Leheste is starting with blindness.
When NYIT’s New York College of Osteopathic Medicine (NYCOM) was established 30 years ago, its major role was to train physicians for medical practice. While that remains the heart of NYCOM’s mission, the school continues to expand its commitment to research.
“It is time for osteopathic medicine to take a bigger role in research development, and at NYCOM we are doing our part,” says Brian Hallas, Ph.D., associate dean of research. “We are assembling a great team of research-oriented clinicians and scientists. Their efforts to build our research program will no doubt elevate NYIT’s recognition and the prestige of our medical school.”
A recent review of research being conducted in NYCOM’s 10 departments shows that there are more than 25 projects underway. The work ranges from a study of balance-control mechanisms in Parkinson’s disease patients to the effects of osteopathic manipulative medicine on gastroesophageal reflux symptoms. Following is a look at three promising projects.
Fishing for Answers
In his molecular biology lab, Leheste, an assistant professor of neuroscience and histology, focuses on genetic research as it relates to human disease. Right now, he’s trying to figure out how to reverse blindness.
One of the leading causes of the affliction is the degradation of photoreceptor cells that respond to light and colors in the neural retina. When light hits the retina, the photoreceptor cells convert this stimulus into an electrical signal and initiate the process that allows us to see. When these cells stop working, so do the eyes.
Leheste has followed the studies of many other researchers who have tried to re-create the damaged cells in order to give back vision—a scientific process that has proven to be, well, impossible. So Leheste is taking a different approach: He is testing whether an altered neighboring cell, the bipolar, can be made to perform the photoreceptor cell’s task. This is where the zebrafish and some pond scum come into the picture.
The protein that the pond scum algae Chlamydomonas rheinhardtii uses to get its share of sunlight (channelrhodopsin-2) is able to create a visual signal much like the photoreceptor cell. By implanting the corresponding gene together with the suitable gene-activator into zebrafish, Leheste’s research will show whether bipolar cells can be used to mimic the naturally occurring light response normally performed by the photoreceptors.
Zebrafish are fast becoming the new genetic research darling because of their uncanny similarity to humans. They are model organisms—that is, their genetic makeup is so similar to humans that in some cases researchers can easily bounce data back and forth from zebrafish to humans.
Researchers have long depended on other model organisms such as mice and rats, but these rodents would never work for Leheste’s research. “The beauty of zebrafish is that they are day vision organisms, similar to humans and a complete contrast to the night vision of rats and mice,” says Leheste. “Plus, they also develop quickly. Zebrafish progress from fertilization to swimming fish in just a few days.”
Heartfelt Help
Charlene D. McWhinney, Ph.D., is looking for a reversal of fortune for her patients as well. But instead of the eyes, this NYCOM researcher wants to heal the heart.
When something goes wrong in the body, it tries to heal itself. Many times this impulse is successful, but when it comes to the heart, it has deadly consequences. One of the heart’s responses to high blood pressure is to start making new proteins. But instead of producing adult proteins, it creates embryonic proteins, meant to work in a child’s body. These are unable to do the job of adult proteins and become weaker and weaker, a process that eventually leads to congestive heart failure.
“What I’m studying is whether there is a way we can alter this process after it has started,” says McWhinney, an assistant professor of biomedical sciences. “The changes so far seem to be irreversible, but I don’t believe that’s true. There was an adult expression of proteins at one time. There’s no reason that we can’t change it back to embryonic.”
Working with rats, McWhinney is studying myocytes—the heart’s primary cells, the ones that cause it to beat. She is also looking at cell signaling from different receptors on the membrane. Then she looks at different signaling pathways that inhibit the process of releasing embryonic proteins.
Because many people with high blood pressure feel perfectly fine, it often goes undiagnosed or patients don’t bother taking the prescribed medications. Eventually they notice the symptoms of congestive heart failure, which include shortness of breath, persistent coughing, swelling, fatigue, rapid heart beat, and irregular heart rhythm. By this point, a downward spiral has begun, and the heart just keeps getting weaker and weaker.
Nearly five million Americans are affected by heart failure, and 550,000 new cases are diagnosed each year, according to the American Heart Association. Cardiovascular diseases are the No. 1 killer of Americans.
“This is a big problem for both men and women, and women don’t realize that after menopause they are just as vulnerable as men,” says McWhinney.
The biomedical scientist, who joined NYIT from Oklahoma State University this year, received a $144,000 grant from the National Institutes of Health to help fund her research.
Timing is Everything
Serendipity rules Linda Friedman’s research lab. She is just as happy to have a hypothesis proven wrong as to have it proven right—it all leads to advancing science.
Her latest results debunk a long-held theory regarding brain trauma and cell death. The findings are so significant she was chosen to chair a symposium on the topic at the Society for Neuroscience’s 2006 conference.
Friedman, Ph.D., an associate professor of neuroscience and histology, began studying the effects of experimental seizures and human epilepsy in 1991, her focus growing so intense in the passing years that she says she lies awake at night thinking about it. When she does close her eyes, she sees pictures of her retinas staring back at her. “But I love it,” she says. “I have the fever, and I believe I always will.”
It has long been believed that the sustained increases in intracellular calcium that follows prolonged seizures or other neurological trauma lead to neurological cell death. Not so, according to Friedman’s research. She has found that the elevated level of calcium in neurons does not always lead to cell death. In fact, she says that under certain circumstances, calcium can even protect neurons from dying. It’s all in the timing.
“We originally thought that if seizure activity began early in life that this would lead to more seizures and brain damage later,” says Friedman. “We now know that this is actually not true.”
When a seizure or other trauma occurs in early life, it can actually produce a long-term tolerance effect, a sort of protection. The same is not true for adults, whose condition worsens with each seizure.
This could lead to big changes in the way treatment programs are designed for seizure patients, says Friedman. Right now, young people receive the same protocol as adults.
Funded by a $75,000 grant from the Partnership for Pediatric Epilepsy Research, Friedman conducted her study by injecting rats with kainic acid to produce seizures at different intervals and then studied how the timing of the seizures impacted potential cell death.
“We found that if we do a series of three seizures with some delay in between while the rat is young, we can get more robust effects,” she says.
As for the role of calcium? Friedman found that early seizures also produced large increases similar to those found in adults, thereby indicating that calcium itself is not the trigger leading to cell death. “There must be some other mechanism or breakdown intracellularly in order for the cells to eventually become vulnerable,” says Friedman.
Interestingly, Friedman’s research shows a tolerant effect if the seizure or brain trauma occurs in the hippocampus (medial temporal) portion of the brain. “But I think that if we understood how this one area of the brain gets protected, then we might be able to protect the other regions as well,” she says. “It’s a big wish, but if I could just resolve one part of the puzzle in my lifetime, then I’ll feel like I’ve made a contribution.”
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Through the looking glass: Assistant Professor Joerg R. Leheste, Ph.D., explores ways to reverse blindness with the help of zebrafish—organisms that share a similar genetic makeup with humans.
Assistant Professor Charlene D. McWhinney, Ph.D., is focusing on proteins that affect high blood pressure and cardiovascular health.
Associate Professor Linda Friedman, Ph.D., hopes her research will lead to a better understanding of how seizures affect the nervous system as well as ways to improve treatment.
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Fellow Basks in the Heat
There are few words a medical school fellow would rather hear than: “Your research has been accepted for publication.” So when John Kafel learned that he was to be published in Brain Research Bulletin, the official journal of the International Behavioral Neuroscience Society, as well as invited to present a poster on his research at the Society for Neuroscience’s 2006 convention in Atlanta, he knew it was going to be a good year.
“After devoting six months of your life to something, it’s amazing to see it pay off,” says Kafel, who rated first-author distinction for the paper titled, “Blood content modulates the induction of heat shock proteins in the neurovascular network.”
Kafel, in conjunction with professors Brian H. Hallas, Ph.D., and German Torres, Ph.D., is studying heat shock proteins in hopes of developing new ways to treat strokes and heart attacks. Heat shock proteins (HSPs) protect cells against external stresses. Once a stressor or injury is detected, they initiate a cascade to rapidly remove damaged cellular components and synthesize new ones. Kafel’s research focused on how blood is involved in this cascade. “Interestingly, we found that blood content plays a vital role in initiating this cascade,” he says, “and whatever marker, protein, substrate, or substance that is responsible for initiating this is present in both the plasma and cellular components of blood.”
With this initial success to buoy them, the researchers are continuing their work.
Kafel said this introduction to research gave him a greater understanding of medicine and will help make him a better doctor. He plans to graduate from NYCOM in May and continue his studies with the hopes of becoming an anesthesiologist. He chose this specialty because it combines the dexterity needed for surgery and the cerebral challenges of internal medicine. “When people need an anesthesiologist, they are at their most vulnerable,” he says. “They need an emotional liaison, someone who is solely concerned with helping them through the procedure. I want to be that person.”
The fellow is grateful for the support and guidance he received from his mentors. “I can’t say enough about Drs. Hallas and Torres,” says Kafel. “Both of them have been vital to my growth as a medical student, a scientist, and as a person. I can’t thank them enough for all they have done for me and all that we have accomplished together.” |
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