2016 SRF Summer Scholar Profile: Alicia Lee

Alicia Lee

SRF Summer Scholar, Class of 2016

Wake Forest Institute for Regenerative Medicine

I recently graduated from Rutgers University, New Brunswick with a Bachelor’s Degree in Biomedical Engineering with a concentration in Tissue Engineering. During my time at Rutgers, I worked under the supervision of Dr. David Shreiber to investigate the mechanical and biological effects of acupuncture so that these mechanisms can be understood and potentially be incorporated into other medical treatments. The Shreiber lab has developed a unique model of acupuncture therapy using acupuncture needle stimulation of collagen gels that mimic loose connective body tissue. I helped refine this model so that it yielded more consistent and reproducible results. I also developed a successful protocol for creating and testing cellular gels so that our model more closely mimicked natural tissue and thereby allowed us to better simulate the mechanical and biological effects of acupuncture therapy.

Additionally, last summer, I interned at the Johns Hopkins Institute of Nanobiotechnology, where I fabricated and developed drug-loaded nanofiber-hydrogel composites to inhibit cancer stem cell migration after tumor resection and thereby prevent metastasis. Under the supervision of Dr. Hai-Quan Mao and Dr. Jisuk Choi, I evaluated the biological effects of the composites and worked with the lab’s collaborator to design a protocol for testing the composites in rats. The drug-loaded composites showed promising results when tested in cell culture, but the animal study was inconclusive. Consequently, there are other studies currently underway to further evaluate the therapeutic effect of these composites. My research experiences have motivated me to learn more about and to contribute to innovations in regenerative medicine and cell-based therapies.

Optimizing the Formation of Renal Tubules in 3D Cell Culture

This summer, I will be working with Dr. Anthony Atala, Dr. James Yoo, Dr. In Kap Ko, and Jennifer Huling at the Wake Forest Institute for Regenerative Medicine towards creating an implantable tissue construct that restores function to damaged or diseased kidney tissue. Chronic Kidney Disease (CKD), which is the gradual loss of kidney function, is an increasingly prevalent condition that often develops into End-Stage Renal Disease (ESRD), an extremely debilitating condition which results in multiple organ failures. Currently, CKD and ESRD patients are treated with either dialysis or kidney implants, but these methods have severe limitations. Although dialysis filters toxins from patients’ blood, it cannot replicate several important functions of the kidney and is not a curative treatment. Furthermore, the average life expectancy of dialysis patients is 5-10 years [1]. Kidney transplantation is currently the only curative treatment, but the critical shortage of available donor kidneys has resulted in waiting times of over 3 years, and graft recipients often experience acute rejection and graft failure [2]. Therefore, there is a need for a comprehensive, biocompatible, and widely available treatment that restores kidney function.

One solution is the creation of tissue-engineered constructs that restore function to damaged or diseased tissue. These constructs can either be partial constructs (which augment the function of existing tissue) or complete constructs (which can completely replace existing tissue). One major challenge in engineering 3D tissue replacements is vascularization, or the incorporation of a blood supply. Pre-vascularization of constructs is critical for cell survival and tissue function. The Kidney Group at WFIRM has done extensive work in developing pre-vascularized partial kidney constructs that have a high degree of vascularization, which can improve the viability of cells in these constructs. Another major challenge is ensuring that the kidney cells in the 3D renal constructs are able to grow, proliferate, and perform their desired functions. Kidney cells in 3D culture tend to self-assemble into renal tubule segments, which are the functional components in normal kidneys (See Figure 1). My project will be “Optimizing the Formation of Renal Tubules in 3D Cell Culture.” I will be seeding renal cells into collagen gels and experimenting with different renal cell concentrations, collagen concentrations, and growth factors to determine which parameters will promote the quickest and the most efficient formation of renal tubules. I plan to incorporate these parameters with the Kidney Group’s pre-vascularized constructs to create optimized partial renal constructs.

Figure 1. Renal tubule self-assembly after 10 days in 3D collagen gel culture at 100x and 400x magnification.

Sections were stained with H&E, staining cell nuclei dark blue and the collagen gel pink. Tubule structures are visible throughout the entire collagen gel and can be identified by the hollow, gel-free lumen formed inside the cells (arrows).

Future Plans:

After my internship at WFIRM, I hope to work in Singapore before returning to the US to pursue a graduate degree. I plan to eventually pursue either a PhD or an MD/PhD degree, and I seek to combine my interests in regenerative medicine and marine biology. I am especially interested in the work that scientists have done in isolating cytotoxic factors from shark immune cells to treat human cancer and in investigating the unusually rapid and wound-free healing process in sharks to see if it can be applied towards humans.

References:

1. Ko, In Kap, Mahran Abolbashari, Jennifer Huling, Cheil Kim, Sayed-Hadi Mirmalek-Sani, Mahmoudreza Moradi, Giuseppe Orlando, John D. Jackson, Tamer Aboushwareb, Shay Soker, James J. Yoo, and Anthony Atala. “Enhanced Re-Endothelialization of Acellular Kidney Scaffolds for Whole Organ Engineering via Antibody Conjugation of Vasculatures.” Technology 2.3 (2014): n. pag. 1 Sept. 2014. Web. 18 Apr. 2016

2. Song, Jeremy J., Jacques P. Guyette, Sarah E. Gilpin, Gabriel Gonzalez, Joseph P. Vacanti, and Harold C. Ott. “Regeneration and Experimental Orthotopic Transplantation of a Bioengineered Kidney.” Nature Medicine (2013): n. pag. Nature Medicine. Nature Publishing Group, 14 Apr. 2014. Web. 29 Apr. 2016.

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