Surgery Research ENews


Volume 4, Issue 2: June 2009

Feature article: Dr. Shireman

research news photo Paula K. Shireman, MD
Associate Professor of Vascular Surgery

We are seeking successful strategies for muscle regeneration — ultimately improving survival rates in traumatic injuries.
Dr. Shireman's lab studies the interactions of bone marrow-derived cells and tissue-specific stem/progenitor cells on skeletal muscle regeneration and angiogenesis (the process of developing new blood vessels). Skeletal muscle exhibits an amazing ability to regenerate as humans grow and sustain injury. In fact, sarcopenia, or muscle loss with aging, is an inability to regenerate muscle in equal measure to the injury sustained by muscle during normal activities.

In their studies, they have used several mouse models: hind limb ischemia, toxic injury and tibialis anterior muscle defect to derive a more complete understanding of how angiogenesis and muscle regeneration occurs after injury. A better understanding of how muscle regenerates could be used to recapitulate this complex process to provide soft tissue coverage after traumatic injury.

Tissue engineering strategies utilizing skeletal muscle offer a unique opportunity to advance the field of regenerative medicine. Most research has been performed in injured brain, spinal cord and cardiac tissues — three tissues that do not normally regenerate in adults. In addition, most patients with cardiac and brain diseases are elderly with multiple comorbidities that are also associated with impaired tissue regeneration.

Alternatively, skeletal muscle regenerates throughout the lifetime of humans and importantly, young patients after civilian and military trauma can experience extremity injuries that require soft tissue coverage for limb salvage. Adult myogenic progenitor cells can easily be isolated from individual patients, thus, there is a readily available source of progenitor cells and a need for skeletal muscle regeneration in young patients with few comorbidities. Furthermore, successful strategies for muscle regeneration in young patients may provide insights that may improve regeneration techniques in elderly patients and in tissues that do not regenerate in adults. Surgeons can play an important role in this process.

Bone marrow can be used to regenerate muscles and capillary networks in injured patients.
Recent findings in Dr. Shireman's research indicate that CC chemokine receptor 2 (CCR2) is important in cellular chemotaxis and recruitment. Dr. Shireman recently published (Sun et al. FASEB J 2009 Feb; 23(2):382-95) that CCR2 expression on bone marrow-derived cells, but not cells that are located within the tissues, was critical for skeletal muscle regeneration. Defects in bone marrow-derived cell recruitment, such as macrophages, stem cells, etc., are an important link in understanding muscle regeneration, as bone marrow biopsies can be performed on patients and autologous adult stem cells from the bone marrow can be used to regenerate muscles and capillary networks in injured patients.

When Dr. Shireman is not advancing the frontiers of science, she focuses on her family:
When asked what she does in her spare time, Dr. Shireman's first response was, "Write grants!" But when no grants are due, she spends time with her husband and 3 children, Patrick and Paul, age 7, and her daughter Aine, age 5. Dr. Shireman is a 'Soccer Mom' on weekends and has been known to frequent the Sea World water park during hot summer days without permanently losing a child.

Dr. Shireman's children have attended the San Antonio Chinese Culture Institute since 2006. The goals of this organization are to introduce Chinese culture through activities and instruction in Mandarin Chinese. As she is a multi-generational American being able to trace roots back to the Revolutionary War, it is exciting for her to learn with her children about another culture. The family has many wonderful Taiwanese friends and have all grown from our experiences. Further, she can't wait until the children are older and can act as translators for future family trips!

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research resident

Mark Muir, MD
Research mentors: Stephen M. Cohn, MD, Trauma Surgery, and Joel Basemen, PhD, Microbiology, University of Texas Health Science Center San Antonio

Current research: Mycoplasma pneumoniae infection in ventilator-associated pneumonia and acute lung injury. Dr. Muir is the recipient of NIH T-32 funding, as well as a Doris Duke Clinical Research Fellowship. His research is conducted at both the UT Health Science Center San Antonio and University Hospital in San Antonio, Texas.

This research project could greatly affect the care of critically ill surgical patients, in particular those patients requiring prolonged mechanical ventilation. The results of this study could lead to improvements in the diagnosis and treatment of pnuemonia in severely injured trauma patients, and perhaps in other arenas of critical care as well.

Current research results suggest that a significant number of ICU patients undergoing bronchoscopy have a pulmonary Mycoplasma pneumoniae infection. The prevalence of mycoplasma in this ICU population is similar to that observed among other cohorts with various chronic lung diseases, but the clinical relevance of these findings remains to be elucidated.

Life away from the lab
Most of Dr. Muir's free time is spent with his wife and their two little girls (the younger one was just born this past December). He's also enjoyed having time to catch up on his reading in areas not related to medicine.

During the past fall and summer, Dr. Muir played on a recreational league softball team. The rewarding moment came in the last game of the regular season when they got their first win. But, tragically, Dr. Muir was sitting out the game with a knee injury. He's also started jogging again, something he really enjoys but hasn't done regularly since medical school.
More about Dr. Muir

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research resident Shaun Gifford, MD
Research mentor: Lt. Col. Todd Rasmussen, MD, Vascular Surgery, Wilford Hall USAF Medical Center, Lackland Air Force Base, Texas
Dr. Todd E. Rasmussen went to undergraduate school at the University of Kansas, followed by medical school at the Mayo Clinic in Mayo, MN. He took an HPSP scholarship and did his residency in the Air Force at Wilford Hall Medical Center. He completed his vascular surgery fellowship at the Mayo Clinic and was appointed assistant professor at the Uniformed Services Medical School in Bethesda, MD. After a few years of clinical practice, Dr. Rasmussen transferred to Wilford Hall Medical Center where he became the chief of the Vascular Surgery Division. He has deployed twice to Operation Iraqi Freedom as a vascular surgeon and has brought his experience home to the lab. He now runs a very productive vascular trauma research lab with three residents, two clinical nurses, and a technologist who work on several projects. Dr. Rasmussen is widely published in trauma and vascular journals, has been invited to speak all over the world, and is devoted to mentoring residents through their research.

Current research: Dr. Gifford is the recipient of a $250,000 US Air Force Surgeon General research award; his research is conducted at both Wilford Hall USAF Medical Center and the US Army Institute of Surgical Research at Brooke Army Medical Center, Ft. Sam Houston, Texas. His research focus has been on the use of temporary vascular shunts to restore blood flow to an injured limb, as well as on ischemia reperfusion and the temporal impact of flow restoration on injury.

The impact of Dr. Gifford's work has direct applicability to trauma and vascular subspecialties. Through his projects, Dr. Gifford has been able to show that not only is early restoration of flow beneficial, but that the use of a synthetic tube early in care to limit ischemia has no harmful effects, and may actually improve outcomes.

Historically, shunts have been utilized in specific instances of limb ischemia and reserved for the most difficult situations. The current war in Iraq has witnessed a volume of extremity vascular injury not seen since the Vietnam War. In close connection to this, the use of the temporary vascular shunt has grown immensely. From these experiences and his research, he now believes that shunts have more of a benefit then once perceived, and that they should be placed earlier in the care of an ischemic limb. Drs. Rassmussen and Gifford hope that their findings will push surgeons to deal with extremity injury more aggressively and not approach limb ischemia casually by allowing the historically accepted "6 hours" of warm ischemia prior to intervening.

In the past year or two what is the most important/interesting/exciting finding in your research?
Prior to his studies, the only literature that existed concerning temporary shunts was based upon feasibility and case series with the likely conclusion of "in a pinch, it seems to work." There was little evidence from a scientific standpoint looking at temporal effects or actually looking at the outcomes after use.

Both of Dr. Gifford's research projects incorporated these questions. The research team were able to scientifically show that delaying placement (or reestablishing flow later and allowing for longer ischemic times) led to worse injury. Although intuitive, this had not been shown before. More importantly, and actually a little more exciting, was the fact that they were able to show that shunt use did no harm. Opponents have been discussing for years the problem with shunt placement. Their fears concerned the expertise needed, the potential for dislodgement, the injury to the intima from shoving a tube in a vessel, among others. In Drs. Rassmussen's and Gifford's follow-up study, they showed that there was no added detriment in patients who had shunts utilized, and in fact, some individuals did better.

What made it better was that these shunts were placed in a tent in Iraq by general, trauma, and orthopaedic surgeons.... without vascular training and they still did no harm!

These results were presented in Tucson at the Southern Association for Vascular Surgery (one of the oldest vascular meetings) and Dr. Rassmussen and Dr. Gifford received nothing but praise.

Life away from the lab - relaxing and having fun
"Fun...? I guess not being on call Q3 and not having to wake up at 5 am 6 days a week is fun enough! All kidding aside, I have spent a lot of time with my family (ife Loretta, daughter Catherine (5), and son Brayden (3)). They keep me pretty busy and it is nice to spend time with them when I am not exhausted. I have introduced them to tent camping at Canyon Lake and we have gone a bunch of times...they love it."

Also, Dr. Gifford has brushed up on his golf game a bit. He still needs some practice and hopes to work out a good schedule next year to get in a few holes a week...or not.

Dr. Gifford says that the non-scientific rewards of his research experience has been to be a good dad and husband with the extra time he's had available to spend with his family, i.e., being normal again. Dr. Gifford feels that residency is great and there are so many interesting things happening. That being said, the residency years are hard on a family because of the enormous time commitment. Taking a break, slowing down, and doing the normal family thing was the best.

Dr. Gifford started his residency not interested in research and planning to plug right through it. Due to some special circumstances with his son, he needed to take some time with his family, and decided to roll the family's needs into the research time. According to him, it was the best decision he ever made — maybe it couldn't be called 'interesting', but for Dr. Gifford and his family, it has definitely been rewarding.
More about Dr. Gifford

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Welcome our new 2009-2010 Research Residents:

research resident Richard Oppeltz, MD
Research mentor: Martin Schwacha, PhD, Professor, Division of Trauma and Emergency Surgery, University of Texas Health Science Center San Antonio Department of Surgery. More information about Dr. Schwacha
Research project: Immunoinflammatory response to burn injury
Research laboratory: Trauma Immunopathology Research Laboratory

Jason Wells, MD
Research mentor: Paula K. Shireman, MD, Associate Professor of Vascular Surgery, University of Texas Health Science Center San Antonio Department of Surgery. More information about Dr. Shireman
Research project: Dr. Wells will be performing research on the role of bone marrow-derived cells on angiogenesis in skeletal muscles.
Research laboratory: Dr. Shireman's Vascular Research Laboratory

Heather Hancock, MD
Research mentor: LTC Todd E. Rasmussen, MD, Vascular Surgeon, Wilford Hall USAF Medical Center, Lackland Air Force Base, Texas.
Research project: Gabe Burkhardt, MD, Brandon Propper, MD, and Shaun Gifford, MD, members of the Wilford Hall vascular surgery research team, have developed a combat pig model which has now been verified to be representative of a combat wounded. Dr. Burkhardt has been exploring one leg of this model which is the "hemorrhage" portion, which will enable him to determine capability of vascular shunts to protect against loss of muscle viability and functional outcomes in a vascular compromised limb. Dr. Hancock will be assuming the portion of the research project related to fluid resuscitation, exploring the physiologic and functional outcomes of individual animals who have suffered a significant traumatic blood loss and have been resucitated with various items: crystalloid/whole blood/blood alternatives in an effort to ascertain morbidity and mortality outcomes in a controlled situation.
Research laboratory: Wilford Hall USAF Medical Center Vascular Surgery Research Laboratory

2009 Summer Research Medical Students:

The Office of the Medical Dean provides funds to support medical students engaged in research projects with UTHSCSA faculty during the summer break after the first year. Summer stipends are awarded for 5-8 weeks of full-time research. Congratulations to the three UT School of Medicine students who will be participating in Surgery research projects this summer:

Medical student: Jennifer Sasaki
Research mentor: Martin Schwacha, PhD, Department of Surgery, UT School of Medicine at San Antonio
Research project: IL-17 and injury-induced myocarditis

Medical student: Tyler Bloomer
Research mentor: Renata Bastos, MD, Department of Surgery, UT School of Medicine at San Antonio
Research project: Evaluation of the mechanism of action of Botulinum Toxin Type A on Human Mammary Artery Vessel Rings

Medical student: Erin Wait
Research mentor: Steven Wolf, MD, Department of Surgery, UT School of Medicine at San Antonio
Research project: Temperature Variability and Outcomes of the Severely Injured

Medical student: Taylor Dunphy
Research mentor: David Imagawa, MD, PhD, Department of Surgery, University of California at Irvine School of Medicine
Research project: Establishment of a multidisciplinary pancreatic tumor biorepository and integrated clinical database

Research Residents' Reading List:

As a diversion from the rigors of medicine and research, Vice Chair for Research Steve Wolf, MD, has instituted a monthly book club for the residents in research. On approximately a monthly basis a book is assigned for reading which is then discussed as a group. Beyond the reading, the gathering allows both the faculty and residents to interact in an informal capacity and on equal footing, since no one is an "expert". The following books have been read and discussed over the past few months:

Freakonomics: A Rogue Economist Explores the Hidden Side of Everything
This 2005 non-fiction book by University of Chicago economist Steven Levitt and New York Times journalist Stephen J. Dubner has been described as melding pop culture with economics. As of 2008, it had sold over 3 million copies worldwide. (Wikipedia)

Angela's Ashes
Angela's Ashes is a memoir by Irish author Frank McCourt, and tells the story of his childhood in Brooklyn and Ireland. It was published in 1996 and won the Pulitzer Prize for Biography or Autobiography. (Wikipedia)

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2009 Research Funding:

Daniel Dent, MD, General and Laparoendoscopic Surgery - January 2009:
NIGMS Subgrant with University of Virginia ($30,000), SIS multicenter study of duration for intraabdominal infection.

Miguel Fernandez, MD, Medical Director, The South Texas Poison Center, Division of Emergency Medicine - December 2008:
Texas Department of Health ($149,057), EPI-Poison Control Centers.

Kent Van Sickle, MD, General and Laparoendoscopic Surgery - April 2009:
U.S. Surgical ($70,000), U.S. Surgical Fellowship Agreement 2009-2010.

Joshua Walker, CCO, Perfusionist, Cardiothoracic Surgery - February 2009:
NIH Subaward with Transonic, Inc. ($14,976), Validating the Calculation of Mixed Venous Saturation While on Veno-Venous ECMO.

Steven Wolf, MD, Vice Chair for Surgery Research, Division of Trauma and Emergency Surgery - May 2009:
Elizabeth Huth Coates Maddux Foundation ($100,000), Fellowship Program for a resident in Surgery/Regenerative Medicine.


Conferences and events:

July 10-12, 2008, San Francisco, CA

Aug 26-29, 2009, State College, PA

Aug 31-Sept 2, 2009, San Antonio, TX

Sept 3-5, 2009, San Francisco, CA

Sept 6-10, 2009, Adelaide, Australia

Sept 9-12, 2009, Boston, MA

Sept 30-Oct 3, 2009, Orlando, FL

If you have a meeting or event you would like listed, please let us know so that it can be included in the next issue.

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Recently published:

  1. Salazar CI, Sunil T, Villarreal CL, Guerra CM. (2009). Evaluation of a community-driven program to reduce underage drinking and driving. Texas Public Health Association Journal, 61(2):36-39.

  2. Price MA, Cohn SM, Love J, Dent DL, Esterl R. Educational debt of physicians-in-training: determining the level of interest in a loan repayment program for service in a medically underserved area. J Surg Educ. 2009 Jan-Feb;66(1):8-13

  3. Wolf SE. Vitamin C and smoke inhalation injury. J Burn Care Res. 2009 Jan-Feb;30(1):184-6.

  4. Cohn SM, Arango JI, Myers JG, Lopez PP, Jonas RB, Waite LL, Corneille MG, Stewart RM, Dent DL. Computed tomography grading systems poorly predict the need for intervention after spleen and liver injuries. Am Surg. 2009 Feb;75(2):133-9.

  5. Sun D, Martinez CO, Ochoa O, Ruiz-Willhite L, Bonilla JR, Centonze VE, Waite LL, Michalek JE, McManus LM, Shireman PK. Bone marrow-derived cell regulation of skeletal muscle regeneration. FASEB J. 2009 Feb;23(2):382-95.

  6. Alvarado R, Chung KK, Cancio LC, Wolf SE. Burn resuscitation. Burns. 2009 Feb;35(1):4-14.

  7. Bohnenblust ME, Steigelman MB, Wang Q, Walker JA, Wang HT. An experimental design to study adipocyte stem cells for reconstruction of calvarial defects. J Craniofac Surg. 2009 Mar;20(2):340-6.

  8. Venkatachalam K, Prabhu SD, Reddy VS, Boylston WH, Valente AJ, Chandrasekar B. Neutralization of interleukin-18 ameliorates ischemia/reperfusion-induced myocardial injury. J Biol Chem. 2009 Mar 20;284(12):7853-65.

  9. Schwacha MG. Gammadelta T-cells: potential regulators of the post-burn inflammatory response. Burns. 2009 May;35(3):318-26.

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© 2009 The University of Texas Health Science Center at San Antonio Department of Surgery. All rights reserved. Contact us. Volume 4, Issue 2, June 2009.
For more information on any of these articles, please email the Research News editor.