Tag Archives: Research

Brain tumor research follows unusual path

Tom Curran, Ph.D.

A promising therapy to combat brain tumors in children has emerged from a confluence of bold research, scientific insight and luck, a Children’s Mercy research director said Aug. 30 in the latest installment in the UMKC Health Sciences Deans’ Seminar Series.

The research aims to block a pathway that mutant cells often take when forming tumors near the brain stem. The work’s progress and hurdles were detailed by Tom Curran, Ph.D., who is the executive director and chief scientific officer of the Children’s Research Institute and a professor of pediatrics at the UMKC School of Medicine.

His presentation was titled “How mice, sheep, corn lilies and a beer helped children with brain tumors: Targeting the hedgehog pathway in medulloblastoma.”

When he started the hedgehog inhibitor work, Curran already had contributed extensively to the understanding of tumor formation – and knew plenty about mice. He discovered the Fos-Jun tumor-generating complex, and had identified reelin, the gene responsible for reeler, the mutation that makes mice lose muscle control.

Curran wanted to extend his mutation research to the tumors that form during brain development, “so we made the decision that we would take a take a precision medicine approach to medulloblastoma, even though we knew nothing about it at the time.”

He said his team came up with “a very naive concept” for proceeding: to identify molecules involved in tumor formation and then develop inhibitors for them, confirming both the mutations and their inhibition in mouse studies. After cause and prevention were demonstrated in mice, clinical drug trials in humans would follow.

The plan, however naive, has generated significant research success.

“That’s what translational research is about,” he said. “You have to develop a simple model … with milestones that let you know you’re making progress toward the goals.

“The other factor that is really important to this kind of science is luck. You need to be in the right place at the right time.”

The project’s first indication of good timing came quickly.

“Three weeks after we decided we were going to target medulloblastoma, the very first paper came out linking the sonic hedgehog pathway and … these tumors.” (A family of mutant genes with a spiky appearance is called hedgehog genes, and one of those was named after the Sonic Hedgehog computer game a Harvard researcher’s son was fond of.)

Sheep and corn lilies entered the picture when Curran was looking for a hedgehog-path inhibitor to work with and recalled a story about sheep giving birth to one-eyed lambs. What might have been a genetic defect was determined instead to be caused by a chemical in the corn lilies the ewes had eaten. The chemical, named cyclopamine, was found to block the sonic hedgehog path, the effect Curran was looking for. But it also was toxic and eventually seemed unlikely to lead to a suitable drug for humans.

Fortune intervened again when Curran was having a beer with a colleague after a conference in Taos, N.M. The friend was an expert on the sonic hedgehog pathway and referred Curran to another researcher whose team was doing similar work but running out of money for testing. Curran got in touch with the other team and was able to do the testing, which produced good results.

The project also has had its share of challenges to overcome, including recurrence of tumors after initial success in a human trial. That often happens in cancer treatment, Curran said, as drug resistance develops. But a biopsy from that case has provided further information, and trials continue.

Besides his positions at the Children’s Research Institute and UMKC, Curran is the Donald J. Hall Eminent Scholar in Pediatric Research and a professor of cancer biology at the University of Kansas School of Medicine.

Before coming to Kansas City, he led the Translational Brain Tumor Program for a decade at St. Jude Children’s Research Hospital; was deputy scientific director of the Children’s Hospital of Philadelphia Research Institute for another decade; and set up the multi-institution Children’s Brain Tumor Tissue Consortium.

Curran earned his doctorate for studies at the Imperial Cancer Research Fund Laboratories in London. His work has been published in nearly 300 papers and cited more than 50,000 times.

 

 

 

Faris receives UMKC Project ADVANCER award

Third-year medical student Hunter Faris, left, has received a research award to work with John Q. Wang, M.D., Ph.D., Westport Anesthesia/Missouri Endowed Chair in Anesthesia Research.

Third-year medical student Hunter Faris has been selected for a student research award from the UMKC strategic funding award initiative, Project ADVANCER (Academic Development Via Applied aNd Cutting-Edge Research). The program supports research projects of UMKC undergraduate and professional students from underrepresented minorities.

Faris will be working with faculty mentor, John Q. Wang, M.D., Ph.D., Westport Anesthesia/Missouri Endowed Chair in Anesthesia Research, to establish a previously unrecognized mechanism underlying the regulation of neuronal activities. His project, Regulation of Src Family Protein Kinases in the Rat Striatum by Muscarinic Acetylcholine Receptor, could significantly advance the knowledge of receptor signaling and protein kinases biology.

Project ADVANCER is a UMKC initiative to provide students the opportunity to gain experience and build a “track record” in research. That experience will provide students better access to competitive postgraduate training such as residencies or graduate programs and, ultimately, to better employment opportunities.

Students who have identified a UMKC faculty mentor in the College of Arts and Sciences, Department of Geosciences; School of Biological Sciences; School of Computing and Engineering; School of Medicine; or School of Nursing and Health Studies may jointly develop an application for a Project ADVANCER award with their faculty mentor.

Faris and Wang expect to produce results that will be published in a peer-reviewed scientific journal.

Med School scientist receives American Heart Association grant for research study

Mingui Fu, Ph.D.

The American Heart Association has awarded a $154,000 grant to UMKC School of Medicine scientist Mingui Fu, Ph.D., to conduct a two-pronged study that could lead to the development of novel therapies for vascular inflammatory diseases.

An associate professor in the Department of Biomedical Science, Fu has been studying the molecular process that leads to atherosclerosis, a thickening of the artery walls created by the buildup of plaque. Atherosclerosis is a common underlying issue surrounding cardiovascular disease and stroke.

While some therapies have proven beneficial, there are currently no available treatments to reduce the early steps that lead to the formation of these abnormal arterial masses.

Fu’s new study will explore at a molecular level the process by which a particular protein, TRIM65, has been found to target those molecules responsible for regulating inflammation, antivirus and cancers. The research also seeks to determine how the loss of the TRIM65 protein affects the adhesion of those abnormal fatty cells to arterial walls to produce atherosclerosis.

If successful, Fu’s study will define a regulatory pathway of endothelial activation and provide insights for developing new therapies for vascular inflammatory diseases such as atherosclerosis.

Recently, Fu and his research lab at the School of Medicine published a paper in the journal Scientific Reports that revealed the discovery of a novel secreted protein in body fat tissue that displayed a potent anti-inflammatory role in immune cells and vascular endothelial cells. In addition, he also has published a review article in Nature Reviews Immunology about RNA-binding proteins in immune regulation.

According to a 2017 report by the American Heart Association, cardiovascular disease is the worldwide leading cause of death and is an underlying factor in nearly one-third of all deaths in the United States.

Donors set sights on work at Vision Research Center

Situated prominently on the corner of 21st and Charlotte is UMKC School of Medicine’s Department of Ophthalmology and Vision Research Center, a bustling center of excellence within the new UMKC Health Sciences District. Yet, even with the cutting-edge research and advanced academics taking place under its roof, many are unaware of the critical position it plays in improving the treatment of eye disease for people in our community and beyond.

Nelson Sabates, M.D., professor and chairman of the Department of Ophthalmology and co-director of the Vision Research Center, is working to heighten the facility’s recognition and its continued efforts to offer the most advanced academic environment for teaching the next generation of ophthalmologists.

Two recent gifts from donors, one from the estate of Mary Adams and the other from an anonymous contributor, are helping to make this goal possible by supporting basic science research being conducted by UMKC faculty members, Peter Koulen, Ph.D., and Karl Kador, Ph.D.

“These gifts will have a significant impact on our ability to provide newer and longer lasting treatments for patients diagnosed with glaucoma, macular degeneration and diabetic retinopathy,” Sabates. “We are grateful to have been chosen by these donors as the recipients of their generous contributions to our mission of ensuring patients receive the most advanced medical treatments available.”

Both researchers are working to develop new therapy approaches urgently needed by physicians worldwide to better diagnose, prevent, and treat eye disease and vision disorders.

Koulen, the Felix and Carmen Sabates Missouri Endowed Chair in Vision Research and Director of Basic Research at the Vision Research Center, focuses on therapy development for chronic diseases of the eye and brain. Kador’s research focuses on creating three-dimensional models of the retina that can be used to understand how retinal ganglion cells (RGCs) integrate and form synapses (the point at which a nervous impulse passes from one neuron to another) with their binding partners within the retina. He and his lab are working to develop a functional cell source and transplantation method to treat optic neuropathies such as glaucoma and optic nerve stroke.

“Having an endowed chair in vision research has been instrumental in our ability to conduct research at UMKC and, in order to continue moving forward, we need to raise additional funds for a second endowed chair,” Sabates said.

Sabates will join the UMKC Foundation Board of Directors in July and is resolute in seeing a new health sciences building become a reality.

“I, along with many others, am a true advocate for advancing UMKC’s combined health sciences with a modern, functional space where faculty and students can have access to the latest technologies,” he said. “I am excited to be a voice for the health sciences arena at UMKC.”

Built on a 50-year history, UMKC’s Department of Ophthalmology and the Vision Research Center look to opportunities for future growth in research, education, prevention, treatment and outreach.

Sarah Morrison research award winners announced

Recipients of the April 2017 Sarah Morrison student research awards are (left to right) Jessica Kieu, Shipra Singh, Vishal Thumar, Komal Kumar, and Katherine Suman.

Five School of Medicine’s students have been selected by the Student Research Program to receive Sarah Morrison Student Research Awards. The awards  support support research efforts and help students fund their presentations at conferences and scientific meetings.

The April 2017 recipients are Jessica Kieu, fourth-year medical student, Komal Kumar, fourth-year medical student, Shipra Singh, fourth-year medical student, Katherine Suman, sixth-year medical student, and Vishal Thumar, sixth-year medical student.

Sarah Morrison award recipients are reviewed by a committee of faculty judges and processed through the school’s Office of Research Administration. Awards of up to $1,500 are presented each April and October. Since 2013, students have received more than $61,000 in financial support from the Sarah Morrison program to support research projects at the School of Medicine.

Students interested in the Sarah Morrison Research awards are encouraged to apply prior to the April 1 and Oct. 1 deadlines each year. For complete application information, visit the Office of Research Administration’s student research website.

Award winners, abstract titles and faculty mentors

  • Jessica Kieu, “Maternal-fetal reactions to acute emotional stress in prenatal depressed mothers: correlations with fetal biomagnetometry measures,” Prakash Chandra – TMC
  • Komal Kumar, “Pregnant Women with Previous Mental Health Disorders and Behavior During Ultrasound,” Prakash Chandra – TMC
  • Shipra Singh, “The Effect of NAAA Gene Expression on Acetaminophen Hepatotoxicity,” Shui Ye – CMH
  • Katherine Suman, “The role of innate immune system signaling pathways in glaucoma pathogenesis,” Peter Koulen – Vision Research Center
  • Vishal Thumar, “Visualizing the Difference between Life and Death: A Comparison of Liver Ultrasound Findings in Children with Sinusoidal Obstruction Syndrome After Bone Marrow Transplantation,” Sherwin Chan – CMH

 

 

Vaidyanathan presents research at international neurology conference

Medical student Vaishnavi Vaidyanathan, right, presented her research poster with her mentors Harold Morris, M.D., and Angela Hawkins, M.S.N., R.N., at the 2017 American Academy of Neurology conference.

Fifth-year medical student Vaishnavi Vaidyanathan spent nearly two months exploring the histories of stroke patients and the effects of the clot-busting drug tissue plasminogen activator (tPA). The result was a research poster she recently presented at the 2017 American Academy of Neurology conference in Boston.

Her presentation showed that patients treated with tPA within the first 24 hours of a suffering a stroke have significantly fewer early onset seizures.

Vaidyanathan began her study last September while completing a neurology rotation at Saint Luke’s Hospital. Under the guidance of Saint Luke’s neurologist Harold Morris, M.D., and Angela Hawkins, M.S.N., R.N., stroke program manager, Vaidyanathan reviewed the histories of nearly 1,300 stroke patients.

“They allowed me to write it up and go through process with their guidance,” Vaidyanathan said. “I learned so much from that, literature searching, how to write up an abstract, doing bio-statistics. It was a great learning opportunity.”

The annual neurology conference in Boston drew an international audience of nearly 14,000 physicians and scientists.

“This conference was a great experience,” Vaidyanathan said. “I got to meet people who are celebrities in the neurology field. They’re very well-known. I had the opportunity to listen to talks about the latest research that’s going on in neurology and hear all the great innovations that are happening. It was an awesome experience.”

Vaidyanathan said she already has ideas for future studies that look at the effects of tPA and other intra-arterial interventions on the incidence of post-stroke seizures.

“I hope to do further investigation of these patients and get more results that I can write up and present,” she said.

Randall selected to NIH research fellowship

Grant Randall

Grant Randall, a fifth-year medical student, has been selected to take part in a student research fellowship program at the National Institutes of Health.

Beginning this June, Randall will take a leave of absence from medical school to devote his full-time focus to NIH’s Medical Research Scholar’s Program. He is the fourth student from the School of Medicine chosen to participate in the program.

“I talked to some of our students, Blake Montgomery and Dean Merrill, who did this NIH program and they had fantastic things to say about it,” Randall said.

The yearlong program offers medical, dental and veterinary students an intensive research fellowship participating in basic, clinical and translational research at the NIH’s campus in Bethesda, Maryland. Randall said he is excited about the prospects of working with and learning from some of the top researchers in the country.

“You get to take part in lectures pretty much every day and do basic science research, often with Nobel Laureates,” he said. “They do leadership classes, classes on statistics, how to conduct clinical research, writing research papers. Basically, a lot of the skills that people typically pick up along the way (in medical school and residency), they teach you there.”

Randall will spend the first couple of weeks of his fellowship meeting many of the NIH researchers and mentors to get an idea of the opportunities available and find a research project that meets his interest. He said he hopes to work in translational research to get a taste of both basic science and clinical research.

He acknowledged School of Medicine mentors Michael Wacker, Ph.D., assistant dean for medical student research, and John Foxworth, Pharm.D., professor of medicine, for encouraging him to explore the NIH program. Randall said he became interested in research while taking part in out-of-town clinical electives and working with scientists at the University of Iowa on immunology projects.

“That was my main exposure to in-depth basic science research, being in a lab every day,” Randall said. “I loved it and decided I wanted to do more.”

Research Summit winners announced

The Office of Research Administration has announced four School of Medicine winners for their poster presentations at the 2017 UMKC Health Science Research Summit on April 26, including a first-place tie.

Sixth-year medical student Kayla Briggs and fifth-year medical student Sai Vanam were each awarded first place for BA/MD students. Clair Smith, a fifth-year student, was awarded second place in the competition.

First prize for non-BA/MD student presentations was awarded to Yashashwi Pokharel, MD, MSCR.

Awards for the winners were provided in memory of former School of Medicine faculty member Loredana Brizio Molteni, MD, FACS.

School of Medicine students presented 51 posters at the event. Each presentation was judged by members of the faculty. This year’s judges were: Darla McCarthy, PhD; Jeffrey Price, PhD; Maria Cole, PhD; Kim Smolderen, PhD; Raymond Scott Duncan, PhD; Jannette Berkley-Patton, PhD; Mian Urfy, MD; Lakshmi Venkitachalam, PhD; Nilofer Qureshi, PhD; Felix Okah, MD, Peter Koulen, PhD; Bridgette Jones, MD; Karl Kador, PhD; Dan Heruth, PhD; Mary Gerkovich PhD; James Stanford, MD; Rosa Huang, PhD; and Paula Nichols, PhD.

The Office of Research Administration also acknowledge Tim Hickman, MD., MPH, for helping students prepare by conducting sessions prior to the research summit and John Foxworth, PharmD, for reviewing the student posters.

All of the student posters presented at this year’s research summit can be viewed on the Student Research website.

Health Sciences Student Research Summit
School of Medicine Winners

BA/MD Student awards
First place (tie)

Kayla Briggs, “Development of a Hepatopancreatobiliary Surgery Tertiary Referral Center within the Veterans Affairs Medical System: Early Experiences.” Mentor: Farzad Alemi, MD, MS.
Sai Vanam, “Effects of Cryopreservation on Structure and Quality of Corneal Tissue.” Mentor: Peter Koulen, PhD.
Second place
Claire Smith, “The Cost and Potential Avoidability of Antibiotic-Associated Adverse Drug Reactions.” Mentor: Jennifer L. Goldman MD, MS.

Non-BA/MD Student Award
First place

Yashashwi Pokharel, MD, MSCR, “Heterogeneity in Treatment Effect in Patients with Peripheral Artery Disease: Insights from the CLEVER Trial.” Mentor: Kim Smolderen, PhD.

Summit spotlights continued growth of student research

Chizitam Ibezim, a third-year medical student, presented his poster at the 2017 UMKC Health Sciences Student Research Summit.

A rapidly growing number of UMKC School of Medicine students are turning an eye toward the future and taking an active role in research opportunities.

That was on display at the latest Health Sciences Student Research Summit that took place on April 26 at the UMKC Student Union. Students from the School of Medicine presented a record number of research posters.

Paula Nichols, Ph.D., associate dean for research administration at the School of Medicine, said students are becoming more aware of the importance of medical research and how clinical practice and research are intertwined. It can also greatly enhance post-graduate opportunities, she said.

Third-year medical student Akash Jani discusses his research poster with Paula Nichols, Ph.D., associate dean for research administration.

“These students are incredibly driven and motivated,” Nichols said. “To get into the more competitive residencies, you need to have completed a quality research project. I think students are looking at their future and saying, ‘I can do extremely well on the Step 1 and Step 2 Boards, but what’s going to help me step forward?’ Having a quality research project that they can discuss in their residency interviews will really help them.”

Students from the schools of Dentistry, Medicine, Nursing, Pharmacy, Biological Sciences, and Computing and Engineering participated in the event . The School of Medicine had the largest representation with 42 medical students presenting 46 research posters with five additional posters from outcomes researchers participating in the school’s masters programs.

Fifth-year medical student Fedra Fallahian presented a poster on the management challenges for medical complex children with cleft lip and palate. She began taking part in basic science research during her second year of school and has already given oral presentations on other projects at conferences in Las Vegas and Boston.

This was her first poster presentation on a clinical research project.

“It’s really interesting because you learn about something in the classroom and a lot of times you think this is so rare I’m not going to see this again,” she said. “Then you see the clinical correlation and the science behind it and the way the patient presents. It’s really exciting.”

She said her research mentors have been important in her growing interest in research.

“They’ve been so supportive of me and so invested in me and my projects,” Fallahian said. “It’s because of them that I like doing research. I definitely want to continue research in my residency and I’m interested in a career in academic medicine, so I’d like to continue with this even with I’m finished with my residency.”

Chizitam Ibezim, a third-year medical student, was presenting a poster that explores a growing wave of patient dependence on narcotics used as medications while recovering from fractures. He said his research has given him a good foundation for when begins his pharmacology class this summer.

“This project looks at a lot of pharmaceutical factors and I haven’t even taken pharmacology yet,” he said. “But this has allowed me to explore that and get a firm foothold into pharmaceuticals, how they’re prescribed and how medications work.”

Nichols said she was impressed with the research projects on display.

“The quality of the projects is amazing when you look at these students and see how well they can discuss the research and talk about the background, talk about the complications and discuss their findings,” she said.

Nichols said Michael Wacker, Ph.D., and Larry Dall, M.D., assistant deans for medical student research, and Agostino Molteni, M.D., Ph.D., director of student research, have been instrumental in getting more students involved in research activities.

“They’ve done an excellent job in coordinating student research and really helping students find the right research project, the right research mentor and placing them in (research) labs,” she said.

Anand presents research at national ACP meeting

Gaurav Anand presented a research poster in March at the National American College of Physicians’ Internal Medicine Meeting in San Diego.

Fifth-year medical student Gaurav Anand took part in the student research poster competition at the National American College of Physicians’ Internal Medicine Meeting. The three-day conference took place in San Diego at the end of March.

In addition to presenting his research poster, Anand attended lectures on topics ranging from radiology to ophthalmology, as well as participating in suturing and arthrocentesis workshops.

Anand called the experience both humbling and enlightening.

Anand with his poster at the National ACP student poster competition.

“Being invited to attend and present my research at this National ACP meeting was an enriching experience, not only by attending the lectures and workshops, but also from learning about the groundbreaking research happening across the country,” he said.

Anand presented his poster, Pharmacological control of oxidative stress-mediated effects on endocannabinoid signaling pathways. He conducted his research at the Vision Research Center with Peter Koulen, Ph.D., director of basic research and Felix and Carmen Sabates Missouri Endowed Chair in Vision Research; and Christa Montgomery, Ph.D., research scientist at the Vision Research Center.

Anand earned a spot in the national poster competition last September when he won the student poster competition at the annual meeting of the Missouri chapter of the American College of Physicians.

After winning the Missouri competition, Anand continued his research prior to the national meeting. He said he is gathering data from the most recent experiments and had not made any major alterations to his poster or abstract.

Anand said he plans to continue his research efforts throughout medical school and his residency training.

“Research is the foundation on which new discoveries are made,” he said.