|Short bowel syndrome occurs in children with an inadequate length of intestine to maintain normal digestion and absorption. These children are dependent on intravenous nutrition to sustain normal growth, however, this is associated with significant cost ($100,000 per patient per year) and morbidity, including infection and liver cirrhosis. Although intestinal transplantation for these patients is possible, outcomes are marginal and there are significant side effects associated with life-long immunosuppression. The long-term objective of this project is to engineer functional intestinal tissue that can be used to treat patients with short-bowel syndrome. Specifically, this project will focus on developing a genetically modified intestinal cell that can be grown on a bio-engineered scaffolding and ultimately, implanted into an animal model. The project can be broken down into three specific goals:
(Funded by UCLA Chancellor’s Border Crossing Initiative, Stein Oppenheimer Award, American Surgical Association Foundation)
|The research project is focused on identifying molecular markers to isolate and transplant adrenal cortical progenitor cells as a potential treatment of adrenal insufficiency. A transgenic mouse that expresses the green fluorescent protein in adrenal cortical cells is used as the animal model. The first specific aim employs two strategies to identify candidate adrenal cortical progenitor cell markers: microarray analysis of adrenal cortical cell lines that differentiate in response to temperature change and screening of known stem cell surface markers during the ontogeny of the adrenal cortex. The second specific aim utilizes flow cytometry to sort primary adrenal cortical cells into subpopulations based on their differential expression of surface receptors. These potential adrenal cortical progenitor cells are transplanted under the renal capsule to determine their regenerative potential. These studies will lead to better understanding of the development of the adrenal cortex, as well as a new therapy to treat adrenal insufficiency in a more physiological fashion.
The Dunn Lab
Qianqian Wang (Cassie) is a 3rd year PhD student in Bioengineering at UCLA. In 2012, Cassie received her B.S in Polymer Science and Engineering at Zhejiang University in China. Cassie’s project is about regeneration of both smooth muscle layers and epithelial layers of intestine. She is trying to grow functional intestinal smooth muscle in vitro, and to build the villi structure of the epithelial layer. Cassie likes dancing, watching movies, swimming, and Chinese poetry. She can be reached at .
Steve Lin is a 5th year graduate student in Bioengineering at UCLA. In 2013, he received his Masters in Bioengineering from UCLA. Prior attending UCLA, he studied Mechanical engineering and received his B.S. from National Taiwan University. The focus of Steve’s research is the development of a gut on a chip. More specifically, he is looking at how the human intestinal epithelium responds to a peristaltic flow environment, which is similar to the native environment in the human GI tract. To study this, he has developed a microfluidic device with epithelium cultured inside. The device can induce peristaltic flow inside the cell-cultured chamber. Additionally, Steve is also working on developing a scaffold with villi structure and is looking at how intestinal stem cells differentiate along the villi. Ultimately, he hopes to combine villi scaffold into the microfluidic device to create a gut-on-a-chip model, which more closely reflects the human native intestinal environment. Other than doing research, Steve enjoys reading, watching movie, tennis and heavy metal music while knitting. Steve can be reached at .
Masae Kobayashi is a graduate student with the Biomedical Engineering department at UCLA. She majored in Bioengineering at UC Berkeley as an undergraduate and developed strong interests in tissue engineering and regenerative medicine. To contribute to the goal of tissue engineering in a functional small intestine, her project focuses on studying intrinsic and extrinsic strategies to induce contractile activities in intestinal smooth muscle cells. Other than doing research, she enjoys dancing, eating, and sleeping. Masae can be reached at ()
Joshua Rouch is a 4th year resident in the Department of Surgery at UCLA, with aspirations to pursue a career in Pediatric Surgery. Prior to starting residency, Joshua studied Human and Organizational Development as an undergraduate at Vanderbilt University, and went on to earn his MD at Indiana University School of Medicine in 2012. He is currently spending his 3rd and 4th years of residency working with Dr. Dunn and collaborators focusing on aspects bioengineering related to diseases of the small and large bowel. His project involves transplantation of skin-derived precursor (SKP) stem cells for the treatment of intestinal aganglionosis in a large animal model of Hirschsprung’s disease. The goal of this project is to utilize human SKP cells to advance this treatment to a translatable, human model. He is also working on the optimization of a biodegradable, surgically implantable spring to lengthen intestine for the treatment of Short bowel syndrome. Outside of the lab and operating room, Joshua enjoys an active outdoor lifestyle: cycling, snowboarding, surfing, hiking, traveling, and fighting crime at night.
Andrew Scott is a 4th year resident in the Department of Surgery at UCLA, who hopes to pursue a career in pediatric surgery. He has been a lifelong UCLA fan, studying chemistry and mathematics at UCLA as an undergraduate student, then going on to earn his MD at Charles Drew University/David Geffen School of Medicine at UCLA in 2011. He has spent the last 2 years working with Dr. Dunn and collaborators on human intestinal tissue engineering with a focus on the optimization of human intestinal stem cell in vitro culture. In his free time, Andrew enjoys trail mix, running, playing the piano, writing poetry, gardening, and spending time with family/friends.
Nhan Huynh is a resident in the Department of Surgery at Loma Linda University with aspirations to pursue a career in Pediatric Surgery. Prior to starting residency, Nhan studied Biochemistry-Cell Biology at UCSD and went on to earn her MD at UC Irvine School of Medicine in 2013. She is working with Dr. Dunn and collaborators focusing on the disease process of the small and large bowel. She is working on the optimization of a biodegradable, surgically implantable spring to lengthen intestine for the treatment of short bowel syndrome. Outside of the lab and operating room, Nhan is a pescatarian who loves to eat sushi and ramen. She is always available to meet up for chai lattes and ice cream.
Elvin is the lab manager with the Dunn Lab. He received his BS in Human Biology from UC San Diego in 2010. He has spent the last few years working with Dr. Dunn and collaborators focusing on bioengineered and surgical solutions for diseases of the small and large intestine. He has been involved in the development and implementation of a biodegradable spring device for use in intestinal lengthening and have also looked at the development and transplantation of skin-derived precursor cells for the treatment of neuromuscular dysfunction in the intestine. In his spare time, Elvin enjoys watching the Los Angeles Dodgers, surfing, camping and hiking, traveling, snowboarding, and getting lost in Asia. Elvin can be reached at
Tiffany Yeh is a masters student in the Bioengineering Department at UCLA and will be graduating Spring 2015. She has been working with Dr. Dunn since 2011 and received her BS in Bioengineering at UCLA in 2014. Her current project focuses on studying the small intestinal crypts and engineering a collagen-based scaffold to mimic the microenvironment and regenerate the intestinal epithelium. Besides doing research, Tiffany enjoys exploring new restaurants, traveling, taking photography, and doing DIY crafts and jigsaw puzzles. She will be attending medical school at Penn State University in Fall 2015.
Mohammed is a graduate student at UCLA studying to receive a M.S. degree in Bioengineering. While studying to receive his B.S. in Bioengineering from UC Riverside, he headed an undergraduate research team dedicated to deriving pancreatic progenitor cells from iPS and hES cells. He is currently working under the direction of Dr. Dunn and collaborators in order to achieve the optimal concentration of various growth factors in order to more efficiently derive human spheroid cells from intestinal crypts. Mohammed’s hobbies include: Working on cars, playing video games, and running. He can be reached for questions at: .
Anne-Laure is a graduate intern in the Dunn lab at UCLA. She received her BS in cellular biology and animal physiology in 2013, and she is studying to receive her Masters in Bioengineering from University of Nice in France. Her project focuses on regenerative medicine and more specifically on intestinal tissue engineering. She is trying to get aligned and contractile smooth muscle cells from isolated intestinal strips. Her work involves using biodegradable polymers and natural decellularized scaffolds. Outside of the lab, Anne-Laure likes exploring LA county, eating Mexican food and cookies, going to the beach and surfing. She can be reached at email@example.com.
Smita is a medical student at the David Geffen School of Medicine, c/o 2018. She received her BS in molecular biology and cell development from Stanford, after which she worked in a series of labs at Genentech, the Gladstone Institutes, and UCSF. Smita has been interested in regenerative medicine and tissue engineering since her undergraduate years, particularly in the integration and manipulation of of patient derived tissues into surgical practice. She hopes to contribute to several translational projects in the Dunn lab. Outside of the lab, Smita enjoys cooking, drawing, boxing, and eating all the things. She can be reached at .
Clara is an undergraduate student at UCLA working towards a degree in bioengineering, with a focus in the fields of tissue engineering and regenerative medicine. She is currently focused on studying aspects of tissue culture and bioengineering for the eventual treatment of short bowel syndrome with hopes to make steps toward tissue engineered intestine. Specifically, her project involves an in-vitro culture model utilizing growth factors from the stromal matrix to enhance growth of human intestinal stem cells. Outside of the lab, Clara enjoys boxcar racing, ultimate fighting, and pottery. She can be reached for questions at: .
- Lahar N., Lei N.Y., Wang J., Jabaji Z., Tung S.C., Joshi V., Lewis M., Stelzner M., Martin M.G., Dunn J.C., “Intestinal Subepithelial Myofibroblasts Support in vitro and in vivo Growth of Human Small Intestinal Epithelium,” PLoS One. 2011;6(11):e26898. Epub 2011 Nov 17.
- McClellan E.B., Shew S.B., Lee S.S., Dunn J.C., Deugarte D.A., “Liver herniation in gastroschisis: incidence and prognosis,” J Pediatr Surg. 2011 Nov;46(11):2115-8.
- Qin H.H., Dunn J.C., “Small intestinal submucosa seeded with intestinal smooth muscle cells in a rodent jejunal interposition model,” J Surg Res. 2011 Nov;171(1):e21-6. Epub 2011 Aug 27.
- Lei N.Y., Ma G., Zupekan T., Stark R., Puder M., Dunn J.C., “Controlled release of vascular endothelial growth factor enhances intestinal adaptation in rats with extensive small intestinal resection,” Surgery. 2011 Aug;150(2):186-90. Epub 2011 Jun 29.
- Geisbauer C.L,. Wu B.M., Dunn J.C., “Transplantation of Enteric Cells in to the Aganglionic Rodent Small Intestines,” J Srug REs. 2011 Jun 7. (Epub ahead of print)
- Zupekan, T., Dunn J.C., “Adrenocortical cell transplantation reverses a murine model of adrenal failure,” J Pediatr Surg. 2011 Jun;45(6):1208-13.
- Singh S., Wu B.M., Dunn J.C., “Accelerating vascularization in polycaprolactone scaffolds by endothelial progenitor cells,” Tissue Eng Part A. 2011 Jul;17(13-14):1819-30. Epub 2011 May 6.
- Geisbauer C.L., Chapin J.C., Wu B.M., Dunn J.C., “Transplantation of Enteric Cells Expressing p75 in the Rodent Stomach,” J Surg Res. 2011 Jan 8. (Epub ahead of print).
- Singh S., Wu B.M., Dunn J.C., “The enhancement of VEGF-medited angiogenesis by polycaprolactone scaffolds with surface cross-linked heparin,” Biomaterials. 2011 Mar;32(8):2059-69. Epub 2010 Dec 13.
- Qin H.H., Lei N., Mendoza J., Dunn J.C., “Benzalkonium chloride-treated anorectums mimicked endothelin-3-deficient aganglionic anorectums on manometry,” J Pediatr Surg. 2010 Dec;45(12):2408-11.