Dr. Gendelman discusses UNMC’s Parkinson’s breakthrough

Regents approve clinical and translational research center

Jennifer Larsen, M.D. The creation of a UNMC Center for Clinical and Translational Research has been approved by the University of Nebraska Board of Regents. The center — which was called for in the UNMC strategic plan as part of the effort to increase the medical center’s clinical and translational research capabilities — will help UNMC to streamline and improve its efforts in this area, said Jennifer Larsen, M.D., the new center’s director. “Clinical and translational research is the direction biomedical research is heading,” Dr. Larsen said. “The push is on for scientists to make their research apply to clinical and community settings and it’s vital that UNMC fall in with this trend. This center will help us do that.” Progress report Click here to access the latest report on UNMC’s progress in fulfilling the institution’s 2007-2010 strategic plan. The report also can be accessed on the “Quick Connect” drop down menu on the top of the UNMC Today homepage (info.unmc.edu). Becoming a real player in the world of clinical and translational research is an important step in UNMC’s march toward world-class status, said Chancellor Harold M. Maurer, M.D. “It’s important that we as a campus put an intense effort toward improving our clinical and translational research, which is the direction biomedical research is headed,” Dr. Maurer said. “I thank the regents for understanding the important role this center will play as we commit to improving and becoming a major contributor in this area of research.” The center will allow UNMC to: Evaluate the clinical and translational research resources it has and how or if they need to be improved; Consolidate those resources and establish a clear path of access so they are more transparent to investigators across the campus; Improve communication with and between scientists about clinical and translational resources, research opportunities and potential collaborators who can enhance the development of new interdisciplinary teams; and Develop new educational programs for students, staff and faculty to enhance their clinical and translational research capabilities. The center also strengthens UNMC’s case as it prepares to apply for a Clinical and Translational Science Award (CTSA) from the National Institutes of Health. CTSAs — which only will be awarded to 60 medical centers nationwide — are meant to create a network of institutions focused on clinical and translational research. Currently 24 institutions have CTSAs. To be eligible for a CTSA, institutions must have a centralized structure and governance for support of clinical and translational research, which NIH officials feel will make the translation of research from bench to bedside to community more efficient. “The UNMC strategy for growing the research enterprise requires more emphasis upon clinical and translational research,” said Tom Rosenquist, Ph.D., vice chancellor for research. “The majority of the growth during the recent phase, when we tripled our funding base, occurred in various areas of basic sciences. Now, we need to expand the scope and volume of work among clinicians, in clinical departments and specialty areas. Read more in UNMC Today.

Embryonic Research is Deserving of Focus

(Op-Ed Published in the Omaha World-Herald September 28, 2007)

In a Sept. 23 Midlands Voices article, Dr. Cam Enarson, vice president for health sciences and dean of medicine at Creighton University, argued for more research into the therapeutic potential of umbilical cord-derived blood cells and for the establishments of a Nebraska-based cord-blood bank.

The University of Nebraska Medical Center also is strongly supportive of research in this important area. Indeed, UNMC scientists pioneered studies of cord blood more than 10 years ago, part of the long and continuing history of stem-cell research that has made UNMC a world leader in the science and technology of bone-marrow transplantation. UNMC therefore is uniquely suited to provide scientific and clinical expertise for advancing work in this area.

I must disagree, however, with Dr. Enarson’s assertion that cord-blood research should be undertaken instead of research that utilizes embryonic stem cells. There is no scientific basis for this assertion.

In the science of stem-cell research, as in all other fields, there are disagreements among its practitioners. But the overwhelming majority of scientists who carry out adult or embryonic stem-cell research agree that embryonic stem cells are uniquely able to become any kind of adult cell. This being the case, they also are most likely to be able to provide life-saving, function-restoring therapies when cells have died and cannot replace themselves, as in cases of a stroke or a heart attack.

In the hard-reality world of scientific research, it is now obvious that embryonic stem cells offer unique qualities. Unfortunately, progress in this work is grossly impeded by laws that limit access to human embryonic stem cells for use by the world’s finest biomedical research power: the National Institute of Health. If this were not so, we would be far closer to unambiguously effective stem cell-based treatments for devastating diseases that are currently incurable.

That is not to say that adult or cord-blood cells have no therapeutic potential. This is a worthy line of research that has value quite independent of the erroneous suggestion that cord-blood cells are a reasonable substitute, with potential equal to that of embryonic stem cells.

It is my business to know and understand both embryonic and adult stem cells - I have spent 25 years carrying out basic research in embryonic development. I am a member of the International Society for Stem Cell Research, which is the premier organization for both embryonic and adult stem-cell research in the world. I also am a charter member of an NIH group empowered to evaluate proposals for research that involve human embryonic stem cells and other stem cells.

Based upon my experience as a scientist, I strongly advocate continuing support for both human cord blood and human embryonic stem cells. We owe it to all of those who are desperately ill and who may ultimately benefit from this work.

Dr. Enarson and many other sincere and respectable health care professionals, and many millions of other good people, base their advocacy of cord blood or other so-called adult stem cells not necessarily upon their scientific evaluation of the data, but more upon the premise that the use of human embryonic stem cells requires the destruction of a human life.

But the ethical and moral high ground on this issue is not so obvious.

Embryonic stem cells are taken from embryos that were prepared as part of the process of in vitro fertilization, or IVF, where several eggs (typically about eight) are fertilized in a laboratory dish, then typically two are implanted in the mother’s uterus.

Most of the eggs are not used and are discarded immediately or relegated to a deep freeze. Sometimes, the excess eggs are donated to other infertile couples, but this is not a typical outcomes and is not supported by most IVF parents. Most embryos unfortunately are destroyed, immediately or after several years in the deep freeze, even though 60 percent of IVF parents would donate their excess embryos to research if they could. (Newsweek, July 30, 2007).

There is no outrage directed at the parents or the IVF clinics around the country. And there should be none, since the entire process is part of the amazing technology that permits infertile couples to have babies of their own. Outrage, it seems, is directed only at the scientists who neither create nor destroy any embryos but offer the only possibility of enduring life for these embryos in the service of desperately ill patients.

I say that the scientists have a just claim to the moral high ground.

UNMC beats national funding trends with $80 million in 2006-07

UNMC researchers continue to buck the national trend for diminishing grant funds, bringing in more than $80.2 million during fiscal year 2006-07, an increase over the previous year’s record high of $79.2 million. At a time of declining funds, including cutbacks at the National Institutes of Health, researchers at the state’s only public academic health science center have grown the enterprise.

“The ability of UNMC researchers to buck the national trend for diminishing grant funding over the past four years has been impressive and is a credit to the success of our scientists,” said Tom Rosenquist, Ph.D., vice chancellor for research.

Since 2003, the actual number of NIH research awards made nationally has declined 21.5 percent, Dr. Rosenquist said.

“During the same period, UNMC researchers have fought for and won an increase of 48 percent in total NIH support,” he said. “It could be argued, therefore, that we have beaten the national index of NIH funding by nearly 70 percent.”

UNMC’s research growth is commendable, said UNMC Chancellor Harold M. Maurer, M.D.

“Our researchers have outstanding studies underway that have gained the support of national funding organizations at a time when securing grants, even for the most promising studies, is difficult,” Dr. Maurer said. “UNMC’s research success will continue to grow with the completion of the new research tower and the recruitment of such stellar faculty as the new College of Pharmacy Dean Courtney Fletcher (Pharm.D.), and cancer researchers Michael Brattain and Drs. Hamid and Vimla Band in the UNMC Eppley Cancer Center.”

Dr. Fletcher, who will join UNMC on Nov. 1 from the University of Colorado Health Sciences Center in Denver, has devoted his research and practice interests toward the clinical pharmacology of antiviral agents. His cumulative federal funding as principal investigator is approximately $9.3 million in direct costs, while the cumulative value of federally funded projects on which Dr. Fletcher has worked as a co-investigator is approximately $40 million.

Michael Brattain, Ph.D., joined UNMC on June 1 as associate director of the Eppley Institute, as well as associate director for basic research at the UNMC Eppley Cancer Center. He was formerly vice president for research and chairman of experimental therapeutics at the Roswell Park Cancer Institute. Dr. Brattain is the principal investigator on four grants from the National Cancer Institute, totaling more than $4.5 million. Three of these grants have been continuously funded for more than 20 years, and one is an NIH MERIT Award, which is given to the top echelon of researchers funded by NIH. Dr. Brattain’s team is focused on translational research in colon and breast cancers.

Hamid Band, M.D., Ph.D., and Vimla Band, Ph.D., were recently recruited from Northwestern University and will join UNMC on Nov. 1. The Bands are internationally respected breast cancer researchers and are currently principal investigators on six NCI grants, together totaling more than $8 million. Dr. Hamid Band’s primary appointment will be in the Eppley Institute, and Dr. Vimla Band’s primary appointment will be in the UNMC Department of Genetics, Cell Biology and Anatomy.

Between 2006 and 2007, UNMC funding from the NIH has been stable in spite of the continuing, precipitous decline at NIH, Dr. Rosenquist said. At the same time, UNMC’s total research-funding rose by more than $1 million.

“This is a reflection on the ability of our outstanding corps of researchers to diversify their funding portfolios and attract support from new, non-NIH sources while we ride out this difficult period,” he said.

The success of UNMC’s research enterprise is critical because it fuels the clinical and educational missions, Dr. Rosenquist said. During the 21st century (2000-2007), UNMC generated nearly one-half billion dollars total in gross extramural funding ($464 million).

“These are all dollars that otherwise would not have come to Nebraska,” he said.

The total, in fact, is more than 50 percent above inflation.

“This is a substantial value to the campus, university and Nebraska economy,” Dr. Rosenquist said, noting the total would have been $304 million had UNMC just kept up with inflation.

UNMC’s funding success, however, already stands above its peers.

“By experiencing continuing growth we are overcoming a large-scale national trend for academic health sciences centers, many of which show a decline in funding,” Dr. Rosenquist said.

The most recent data available for UNMC’s Board of Regents peer institutions shows that, between fiscal years 2005 and 2006, six of UNMC’s nine peers experienced a loss of NIH support, with an average decline among the six centers of more than 5 percent. The greatest loss was 13 percent. Only one of UNMC’s nine peer institutions was able to match the 5.5 percent growth in NIH funding experienced by UNMC during 2005-2006.

“Bolstering our research emphasis on selected areas, diversifying our funding sources and placing an emphasis on becoming the best place in the country to do biomedical research is paying off,” Dr. Rosenquist said. “Despite the national funding climate, we are within reach of attaining our next goal of $100 million in research funds.”

Dr. Porter collaborates in NIH-funded microbubble project

TUCSON, Ariz. — UNMC’s Tom Porter, M.D., is working with an Arizona-based pharmaceutical company on a National Institutes of Health (NIH) project examining the affect of microbubbles and ultrasound on blood-brain barrier permeability. Dr. Porter, a professor of internal medicine at UNMC, is the principal investigator on the project, and will work with ImaRx Therapeutics, Inc. of Tuscon on the $950,000 grant from the National Institute of Neurological Disorders and Stroke, a division of the NIH.

The funding comes from a Phase I Small Business Technology Transfer Program (STTR) grant. STTR is a federally-funded program designed to stoke collaboration between private businesses and public institutions

The study is designed to examine changes in the permeability of the blood-brain barrier after being treated with microbubbles and ultrasound over a two-year period. This project will also explore whether certain drugs that cannot get across the blood brain barrier on their own, may be able to cross when delivered with the microbubbles.

“This project will provide the foundation for the noninvasive use of transcranial ultrasound and intravenous microbubbles to target drug delivery across the blood-brain barrier,” Dr. Porter said.

Although vital for normal brain function, blood-brain barrier impermeability presents a problem when treating malignant and degenerative disorders of the central nervous system, such as brain cancer, Alzheimer’s and Parkinson’s disease.

Dr. Porter and ImaRx will evaluate whether microbubbles and transcranial ultrasound can safely enhance drug delivery across the blood-brain barrier. Work will begin on the grant this fall.

Dr. Porter recognized a number of UNMC researchers or clinicians who are assisting him on the study. Yuri Persidsky, M.D., Ph.D., professor, pathology & microbiology and pharmacology and experimental neuroscience, and William Thorell, M.D., assistant professor, neurosurgery, will serve as co-collaborators. Pierre Fayad, M.D., professor and chairman, neurological sciences, and Philip Bierman, M.D., associate professor, oncology-hematology, will serve as consultants. Janina Baranowska-Kortylewicz, Ph.D., professor, radiation oncology, and Thomas Jerrells, Ph.D., are consultants assisting with the analysis of the data. Michael Boska, Ph.D., professor, radiology, will assist with the brain MRI studies, examining how ultrasound and microbubbles alter blood brain barrier permeability.

“We are pleased to be working in conjunction with Dr. Porter, who is a leading authority in the development of treatments using microbubbles with ultrasound,” said Bradford Zakes, president and CEO of ImaRx Therapeutics, Inc. “We believe this research could both help identify new drug delivery product opportunities, as well as complement the knowledge we are gaining on the use of microbubbles and ultrasound to treat patients with acute ischemic stroke.”

ImaRx Therapeutics is a biopharmaceutical company that researches and develops therapies for stroke and other vascular disorders using its proprietary microbubble technology.

Advancing health care together

From the beginning of the 21st century, scientists at UNMC have excelled in two significant areas. Research grants and contracts have doubled and international reputations have grown with the publication of highly important findings in the most competitive journals.

This inaugural issue of UNMC discover describes a small sample of that work, providing a valid snapshot of UNMC’s biomedical research that is likely to improve the duration and quality of human life.

We are in the midst of building our second state-of-the-art, multi-story research facility and UNMC research is thriving, yet there are obvious threats to our ability to continue to grow. As is the case for all academic health centers, most of our research support comes from the National Institutes of Health (NIH).

Recent decisions in Washington, D.C., have resulted in an erosion of NIH support. Now, only one in seven scientists will receive the necessary funding support for a project. As a member of one of the NIH review panels, I have seen the thousands of outstanding projects that will never be completed because of this problem. There is no doubt this funding cutback is preventing thousands of disease-fighting, potentially life-saving discoveries from being made.

At UNMC, we have continued to beat the odds by winning an ever-increasing share of NIH funds and by competing successfully for support from other sources. But ultimately, the problem will have a negative impact upon the greater community of U.S. biomedical researchers and upon the advance of health care. Unless all scientists, and the public at large, join together to insist upon restoration of this monumentally successful and invaluable public resource, progress will proceed at a snail’s pace.

Thomas H. Rosenquist, Ph.D.
UNMC Vice Chancellor for Research

Click here to read discover.

Clinical and Translational Research: Getting into the ring

Recently UNMC has embarked upon a strategic plan to increase clinical and translational research on our 500-mile-wide campus. This is consistent with the remarkable research growth UNMC has enjoyed over the past few years: an analysis of the research activity and funding patterns of the top 100 academic health sciences centers in the U.S shows that the proportion of the research effort devoted to clinical and translational research increases with the total mass of research and research funding. In the lower echelons of health sciences centers, the great majority of research and research funding is in the basic sciences. Ascending the scale includes, in virtually all cases, continuing increases in basic sciences research, with a proportionately greater increase in clinical and translational research.

Although the resources to support us in this great adventure are abundant, the level of competition for winning those resources increases every day. NIH currently is the principal source of research funding for UNMC. NIH funds are distributed about 60 percent to basic research, 25 percent to translational research, and 15 percent to clinical research. UNMC is poised to increase its share of those translational and clinical research dollars, which together amount to about $12 billion per year in 2007 dollars.

In addition to NIH dollars that we can compete for, the pharmaceutical industry currently spends about $60 billion annually on research, about $50 million of which is for clinical and translational research; and half of this total or about $25 billion is distributed by competition among academic health sciences centers and other research-heavy institutions.

To retain our current research growth curve, UNMC must get into the ring and outperform competitors for clinical and translational research support from the NIH, from industry sources, and from federal sources other than NIH. UNMC is poised to make a jump up the scale. Recent changes in the organization of our translational research arm, UNeMED, are a positive step. Another is our assumption of clinical and translational research growth as a major strategic issue for all of UNMC, and the plan is almost complete for kicking off the new UNMC Center for Clinical and Translational Research.

We have both the will and the research talent to retain our momentum. The key to our continuing success is the enthusiasm and support of all of the UNMC faculty and staff.

Retaining researchers

by Tom Rosenquist, Ph.D.
UNMC Vice Chancellor for Research

This is my initial foray into the Blogosphere, it feels so 21st-century. I plan to keep this up, with fairly frequent commentary about the state of the UNMC research enterprise. There will be some objective data provided here from time-to-time, but there are so many varied and accurate sources of data, of all kinds, available at all times and places on your laptop, that any data or statistics I might include are sure to be redundant, less current, and likely to add to the boredom quotient of the writing. Generally I’ll try not to be boring, but you know, I’ve been a professor for 30 years, so it may be an uphill battle.

There are so many important issues impinging, infringing and intruding relentlessly upon UNMC research that it’s a bit difficult for me to select the one issue that is sure to pique the most interest and commentary from the readers (assuming that there are such); so I’ll discuss the topic of an interview I gave to an Omaha World-Herald reporter a couple of days ago, since I’m thinking about that right now, and blogging is said to facilitate the most rapid transmission of immediate issues (I read this in a blog, so you know already that the writer had a pro-blog bias).

The topic of the W-H interview was this: recently a key, well-funded scientist from UNL was recruited to Michigan, along with her spouse who also is an excellent, NIH-funded scientist. Just since 2003, both have been recipients of the prestigious Nebraska University-wide Outstanding Research and Creative Activity Award, AKA “ORCA”. (FYI the other orca is Orcinus orca, a large predatory aquatic mammal; these orcas are like our ORCAs in that they are widely admired for their strength and fearlessness, are at the very top of the food chain in their particular ecosphere, and are relatively rare [for a good example of these qualities, see 2007 ORCA winner, UNMC’s Dr. Alexander Kabanov]).

Articles about the imminent departure of this pair of gifted scientists already have appeared in the Lincoln Journal Star and UNL’s newspaper, the Daily Nebraskan. I’m not sure why this particular event has triggered a flurry of media coverage other than, within our university system, there is a growing emphasis upon recruiting and retaining the best scientists, and the loss of any important scientists is a concern, to be dissected and scrutinized, and the event therefore may be used by us as an occasion for reflection and learning.

It is important to bear in mind that excellent mid-career scientists are the most viable commodities on the academic job market. Typically the best and brightest are the objects of frequent or continuous wooing from other institutions. The most common basis for accepting an offer is some combination of higher salary; increased responsibility and / or independence; increased opportunities for more or more varied, productive research and research collaborations; and the perception of the opportunity for improved institutional, urban or regional geography. Given these features, although we are developing a pro-active program for retaining these good people, it is unlikely that UNMC will succeed 100% of the time. Obviously we do not control and cannot modify the impact of some of them. We do, however, need to understand the threats and opportunities as best we can, and maximize our chances.

Recently Dr. Paula Turpen carried out a survey of UNMC’s top scientists to help understand their concerns, that is, those issues that were most important to them regarding their profession, and therefore, an index of things to be aware of in developing our program for retention. Among both MDs and PhDs, there were some recurring themes, test items that had the most responses as important issues: salary level; critical mass of researchers with shared interests; research infrastructure; availability of top-quality graduate students, post-docs and research assistants. For MDs, time released from clinical responsibilities also was crucial. No other issues were even close to these. Consequently we have made a concerted effort to address, in an effective an expedient way, each of them. In time we will know whether or not we have carried out the appropriate analysis and responded both wisely and effectively, however there is some basis for optimism.

Recently, I attended the ceremony hosted by Drs. Gollan and Zucker, for the 2007 edition of the Joseph P. Gilmore Research Award, which as you know is given to a highly meritorious UNMC scientist in mid-career. The good news is that we are able to keep almost all of the Gilmore award winners here at UNMC: 100% of the 10 most recent winners are here; 12/13 or 92% of the winners over the past 10 years are still here. The Gilmore Award winners at UNMC have stayed to become UNMC, U.S and international leaders in research, and among them are perfect examples of the dynamic, in-demand person described above.

They and other excellent scientists may be here because we are doing the right things to induce them to stay, or because we are very lucky. I suspect it’s a combination of the two. But I hope this blog can be a nexus for dialog, information gathering and further trenchant analysis that will enhance our effort to win the war for the hearts and minds of the alpha-investigators. We want and need to do all we can to keep them happy, healthy and especially, to keep them here.

About Tom Rosenquist, Ph.D.

Tom Rosenquist, Ph.D. is the Vice Chancellor for Research at the University of Nebraska Medical Center.

Dr. Rosenquist received his Ph.D. from the Louisiana State University Medical Center and did post-doctoral work at the University of Southern California . He was a faculty member at the University of Southern California and the Medical College of Georgia before joining UNMC in 1991 as Professor and Chairman of the Department of Cell Biology and Anatomy. He was named UNMC Director of Research Development in 1999, and has served as Vice Chancellor for Research since 2002. Since Dr. Rosenquist became active in UNMC research administration, total research activity at UNMC has risen from about $30 million per year to about $80 million per year.

Dr. Rosenquist is a developmental biologist with special interest in the causes and prevention of congenital heart defects. Currently, he is Principal Investigator of a Program Project Grant from the National Institutes of Health. Since he came to UNMC, he has been awarded grants with a total value of about $11,000,000 in NIH funding to UNMC. He has served as a member or chair of NIH grants review committees for many years. He was a candidate for president of his national academic association in 2005. Currently, he is a member of the Editorial Boards of Developmental Dynamics and Anatomical Record.

Dr. Rosenquist has received awards for his teaching from colleagues, medical students and graduate students. When he was chairman of the Department of Genetics, Cell Biology and Anatomy, the department was named the best teaching department in the Nebraska university system and was awarded the “University-Wide Departmental Teaching Award,” while at the same time the department rose to a “Top 25” national ranking in NIH funding, the highest research ranking among UNMC departments.