(12af) Modulating Antigen-Specific T Cell Immunity with Biomaterials-Based Vaccine

Research Interests: Over the past several decades, biomaterials have been widely engineered for treating or diagnosing diseases such as cancers. My research experience and interests have been focused on using micro/nanofabrication of biomaterials for cancer therapies and diagnosis. In this poster session, I will highlight the major research directions I have been involved in during my graduate and postdoctoral research. The results of these efforts demonstrate my capabilities in using biomaterials for micro/nanofabrication, drug delivery, bio-sensing, and more recently, for vaccine design. Thus far my efforts have led to 21 papers (6 as first author) Building on this training, I will describe my plans to develop a distinct, independent research program at the interface of biomaterial, surface and immunology. Briefly, I plan to build a research lab studying immune detection and biomaterial vaccine for tissue inflammation and fibrosis.

I completed my PhD in Biomedical Engineering at Florida State University in 2013 under the supervision of Dr. Jingjiao Guan. My research was focused on developing non-conventional micro particles with well-defined shapes, diameters and components.[1, 2] These particles have been employed in biomedical applications such as drug delivery, cell tracking, and radiation therapy for cancer.[3-7] Upon completing my PhD, I worked as a postdoctoral researcher at Worcester Polytechnic Institute under the supervision of Dr. Ming Su, studying enhanced radiation therapy of cancer. Briefly, my research focused on modifying gold nanoparticle surface to enhance their uptake by cancer cells. Upon X radiation, X-ray photons in radiation therapy can generate photoelectrons and Auger electrons, which can cause ionization of water and formation of reactive free radicals. These free radicals diffuse through chain reactions in cells, and damage DNA in mitochondria and nuclei by extracting hydrogen atoms from ribose sugars, kill cancer cells by cleaving of the polynucleotide backbone in cancer cells. During this period of time, I gained valuable training in surface modification of biomaterials for radiation therapy cancer.[3, 5, 8, 9] In August 2014, I joined the University of Maryland College Park under the supervision of Dr. Christopher Jewell. My research in the Jewell lab has focused on exploiting biomaterials to generate specific, tunable immune responses.[10, 11] My research in this area has two directions: 1) investigating and understanding how biomaterials impact the structure of major secondary immune organs such as lymph nodes and spleens, and 2) developing biomaterial vaccines for cancer treatment.

Through training in three different labs, I have gained valuable training and experience in grant writing, scientific management and teaching. These experiences will allows me to build and run my future own labs.

References

[1] Wang ZB, Zhang P, Kirkland B, Liu YR, Guan JJ. Microcontact printing of polyelectrolytes on PEG using an unmodified PDMS stamp for micropatterning nanoparticles, DNA, proteins and cells. Soft Matter 2012;8:7630-7.

[2] Zhang P, Guan J. Fabrication of multilayered microparticles by integrating layer-by-layer assembly and microcontact printing. Small 2011;7:2998-3004.

[3] Wang CM, Sun A, Qiao Y, Zhang P, Ma LY, Su M. Cationic surface modification of gold nanoparticles for enhanced cellular uptake and X-ray radiation therapy. J Mater Chem B 2015;3:7372-6.

[4] Zhang P, Xia JF, Wang ZB, Guan JJ. Gold nanoparticle-packed microdisks for multiplex Raman labelling of cells. Nanoscale 2014;6:8762-8.

[5] Zhang P, Qiao Y, Xia J, Guan J, Ma L, Su M. Enhanced radiation therapy with multilayer microdisks containing radiosensitizing gold nanoparticles. ACS Appl Mater Interfaces 2015;7:4518-24.

[6] Kirkland B, Wang Z, Zhang P, Takebayashi S, Lenhert S, Gilbert DM, et al. Low-cost fabrication of centimetre-scale periodic arrays of single plasmid DNA molecules. Lab Chip 2013;13:3367-72.

[7] Liu Y, Kirkland B, Shirley J, Wang Z, Zhang P, Stembridge J, et al. Development of a single-cell array for large-scale DNA fluorescence in situ hybridization. Lab Chip 2013;13:1316-24.

[8] Zhang P, Qiao Y, Wang CM, Ma LY, Su M. Enhanced radiation therapy with internalized polyelectrolyte modified nanoparticles. Nanoscale 2014;6:10095-9.

[9] Qiao Y, Zhang P, Wang CM, Ma LY, Su M. Reducing X-Ray Induced Oxidative Damages in Fibroblasts with Graphene Oxide. Nanomaterials-Basel 2014;4:522-34.

[10] Zhang P, Chiu YC, Tostanoski LH, Jewell CM. Polyelectrolyte Multilayers Assembled Entirely from Immune Signals on Gold Nanoparticle Templates Promote Antigen-Specific T Cell Response. Acs Nano 2015;9:6465-77.

[11] Chakrabarti KR, Andorko JI, Whipple RA, Zhang P, Sooklal EL, Martin SS, et al. Lipid tethering of breast tumor cells enables real-time imaging of free-floating cell dynamics and drug response. Oncotarget 2016;7:10486-97. (cover article)

***Featured on cover of Genetic Engineering and Biotechnology News

Teaching Interests:

 

STATEMENT OF TEACHING PHILOSOPHY

 

With all of the roles that professors play, I consider teaching and mentoring be two of the most important ones. Through these two roles, professors deliver multiple levels of information to students, ranging from professional skills to problem-solving techniques, such as math and logic that can be employed from class room to daily life. With my past experiences as both a student and mentor, I have established skills and a philosophy (see below) that would allow me to train students at different levels (e.g. undergraduate and graduate). Based on these experiences and skills, I will expand my teaching and training activities to my research group, the department and the surrounding community. My teaching plan includes using a variety of teaching tools to deliver scientific knowledge to the students, which will help train another generation of outstanding scientists and engineers.

PAST EXPERIENCE

 

Teach students in accordance with their aptitude. During my Ph.D. study, I served as a teaching assistant (TA) from 2008 to 2011 in courses including Transport Phenomena I (ECH 3204), Mass and Energy Balances I (ECH 3203), Separation Process (ECH3418), Quantitative Anatomy and Systems Physiology (BME4403C) and Lab TA in Quantitative Anatomy and Systems Physiology (BME4403C). Besides routine and impersonal teaching jobs such as grading, other works including office hours and teaching in the lab allowed me to interact with students directly. During these interactions, my responsibility involved helping students find out what was wrong with their homework or experiment and guiding them to understand how and why their thought processes led to the incorrect answer. These works required me to understand how the students used the knowledge to finish their work. What I found interesting was that, while different students made similar mistakes in their assignments, the reasons and logic behind these mistakes were often completely different. For example, some students might do their homework or experiment carelessly and get the wrong answer, while others could make a similar mistake due to insufficient understanding of the knowledge. Through these interactions with students, I established my teaching philosophy to â??teach students in accordance with their aptitudeâ?. This philosophy was further enforced in my other teaching and mentoring experiences.

Establish students with a vision and tangible future plan. I worked as a lecturer for students in a middle school in a rural area of China during summer 2006 and 2007. The goal of this work was to offer children from low income families a chance to improve their studies in Math, Chemistry, and English. What surprised me during these teachings activities was that some kids did not study hard simply because they lacked a vision or a visible future plan that was connected to their studying. For example, one student mentioned to me that he did not need to learn the knowledge since he was born to be labor worker, and that this idea was rooted in his mind by his parents. While this studentâ??s studying attitude changed when he learned how the knowledge could change his future, I questioned how long this change could last. The lesson I learned from this experience was that teaching efficiency can be improved if knowledge is delivered to students alongside a concrete vision so that they can link what they are learning with a tangible future plan.

Visible benefits are important, but so is inherent happiness during learning. I mentored students at different levels since 2008. These mentees included undergraduates from Florida State University, the University of Maryland College Park, and other universities such as the California Institute of Technology. The mentoring process included training students on micro/nanofabrication for different bio-applications (e.g. drug delivery, bio-sensing). In Maryland, I mentored a high school student from Wheaton High School in a program called â??Enhance Participation in Research (EPR, supported by National Science Foundation)â?. In this one year program, the mentee selected a biomedical topic that she was interested in; in turn, the mentor provided feedback throughout the process, from collecting literature to finalizing the topic into a poster and report at the end of the year. In addition to mentoring students in experimental design and data analysis, I also directed an undergraduate in the University of Maryland College Park in writing proposals based on her research, which was funded with an ASPIRE fellowship from the university ($3000). In these mentoring processes, I found that the motivations for students in research mainly came from three sources: future career development, happiness in research, or both. For students driven by future career development (e.g. attending medical school), a project that can develop into a scientific paper is a very effective strategy; as for students driven by the inherent happiness of performing research, a topic that intrigues him/her is very important. For example, my Wheaton High School student was very interested in why her dog was slow and reluctant to move when it got old. While there was not enough literature reported, she learned knowledge by comparing the disease in her dog with Alzheimerâ??s disease in humans. Through this learning process, the student developed a motivation to become a biomedical engineer in college. While both mentees learned a great deal of intellectual information on their respective subjects, they informed me that they gained a joy though the research.

 

TEACHING PHILOSOPHY

 

Teachings, in my point of view, can deliver two fundamental techniques to the students: 1) professional skills in one specific area, and 2) robust problem-solving techniques. For professional skills in chemical and biomedical engineering, the students can be trained with highly refined techniques such as generating micro-devices through photolithography. By obtaining these techniques, the students can start their careers in international companies such as Intel, Eli Lilly and Company, Novartis, and Merck & Co. In addition, while expertise in one specific area can help students to build their professional life, the problem-solving techniques can arm them with common sense skills that can be applied to almost all areas of life. Some of these problem-solving techniques include logic, math, and the fundamental laws of physics and biology. Based on my teaching and mentoring experiences, I would like to help students obtain these techniques through 3 specific teaching tools, as mentioned above: 1) teach students in accordance with their aptitude; 2) establish students with a vision and a tangible future plan; and 3) help students find happiness in learning.

 

TEACHING AND MENTORING PLAN

 

My plan for training young scientists and engineers in my classes and research group will focus on three aspects: 1) Implement problem solving contents; 2) teach and help students according to their career goals and aptitudes; and 3) improve my own communication and teaching skills during interactions with students.

 

Teach in current and future courses. My (previous) training is in chemical and biomedical engineering. I was mostly interested in teaching transport phenomena, mass and balance transport, and physiology. However, I am enthusiastic about any courses that will allow me to interact with students. My teaching will focus on two aspects: 1) the fundamental sciences inherent to the courses, and 2) problem-solving techniques associated with these courses. In addition to conventional teaching in class, the student will be asked to design questions based on the courses for peers, structure a project toward specific problems associated with the course, and compare the potential solutions to the given problems. I will also try to develop new courses relevant to my research. For example, one course will be â??Micro/Nano-Vaccinesâ?. This course will cover the necessary skills and techniques in nanotechnology and immunology and how these two areas interact for novel vaccine development. In this course, students will be introduced to conventional (i.e. emulsion) and non-conventional (i.e. top-down techniques, such as photolithography) methods for generating micro/nanoparticles; students will also learn about immunology and how the micro/nanoparticles modulate the immune system in vivo. At the end of this course, the student will give a presentation on one of the existing vaccines and propose how they will improve that vaccine with micro/nanotechnology.

Advise menteesâ?? research and professional development. Advising my own research group is one of the most exciting responsibilities for me. I am eager to work with students who interact and learn in different ways. My advising activities will include at least two parts: 1) a regular portion to discuss each studentâ??s research project, and 2) a portion that discuss flexible topics that depends on the studentâ??s stage of development. The regular meeting will start with a discussion of research difficulties. Students will not be provided a direct answer; instead, their problems will be answered with other questions. For example, if the student cannot synthesize a polymer particles via emulsion, he/she will be challenged by a series of questions such as: What are the components used in the synthesis? What are the functions of each component? How do these components interact? What is the formulation in other literature? By asking these kinds of questions, the students will be expected to think on their own. The flexible part of the meeting will depend on the studentâ??s need. For example, the senior students may want discussions on how to apply for national meetings, fellowships, or even learn to write grants. The studentâ??s professional plan is also an important part of my advising, in which he/she will create a mutually agreed upon plan including action steps that are to be updated every 6 months.

Improve my own professional skills and technical expertise. Teaching and interacting with students will offer valuable opportunities to improve my own skills as a teacher and expand my technical expertise. For example, the â??Micro/Nano-Vaccineâ? course will expose me to immunology that I have only partially studied in the past, and I will thus use this teaching experience to enrich my knowledge in this area. The experience of guiding students in lab will also allow me to learn how to mentor them effectively. Therefore, through these process, I will become even more effective and responsive to individuals with different backgrounds, research styles, and goals.