Designing Novel Interfaces to Control Beneficial and Pathogenic Microbes

Research Interests:  Bacteria that colonize on medically and environmentally relevant surfaces are subject to a variety of physical forces. For example, in potentially pathological cases, bacterial cells withstand shear stresses along blood vessels and electric discharges near medical implants as they develop infectious, mature multicellular aggregates known as biofilms. And in an environmentally relevant example, oil-degrading bacteria overcome complex interfacial energies to colonize fluid interfaces and establish films of bacteria at (oil-water) interfaces (FBI). My research program exploits fundamental knowledge of the physiological responses of bacteria to physical forces to investigate the development of new interfaces that will both help minimize the deleterious and optimize the beneficial effects of bacterial film formation. The outcomes of this research will inform new biomedical and technical strategies to: (1) eradicate multidrug-resistant (MDR) infections, (2) control microbial dynamics relevant to health and biotechnology, and (3) alleviate the ecological impacts of oil spills.

Research Experience: My research has encompassed interrelated areas ranging from food microbiology, to medical bacteriology and biotechnology. I have investigated how beneficial microbes can contribute to human health, as well as how bacteria are involved in many recalcitrant infections. Over the course of my graduate education, I focused on developing technologies targeting the resistance mechanisms of intrinsically quiescent bacterial cells, called persister cells. I studied how manipulating the electrophysiological properties of P. aeruginosa persisters can sensitize these cells to antibiotics and metallo-drug complexes previously demonstrated to be ineffective against persister cells. My current postdoctoral training builds upon my prior experience to decipher the interfacial properties of bacterial films. I have gained expertise in characterizing 2- and 3-D bacterial films from physical and metabolic standpoints. Now, I am developing artificial microniches as functional microbial nanoculture systems using soft nanomaterials to advance the general understanding of microbial dynamics involved in complex biofilms. The microniches, when further advanced, will have applications for personalized, therapeutic medicine or for high-throughput screening of unculturable microbial species relevant to biotechnology and drug discovery. My research experience and relevant products are highlighted below:

Postdoctoral Training–Supervisors: Kathleen Stebe and Daeyeon Lee, Chemical and Biomolecular Engineering, University of Pennsylvania

Project 1: “Artificial Microniches for High Throughput Study of Microbial Communities.”

1) Niepa THR, Hou L, Jiang H, Goulian M, Koo H, Stebe K, and Lee D (2016) Microbial Nanoculture as an Artificial Microniche (Scientific reports, Accepted).

2) Hann SD, Niepa THR, Stebe KJ, Lee D. (2016).  One-step generation of cell-viable compartments via polyelectrolyte complexation in an aqueous two phase system (Submitted)

3) Kim D., Sengupta A., Niepa THR, Lee BH, Weljie A., Murata R., Stebe K.J., Lee D., Koo H. Candida albicans stimulate Streptococcus mutans microcolony development via cross-kindom biofilm-derived metabolites (In preparation).

Project 2: “Physical and Metabolic Properties of Films of Bacteria at Fluid Interfaces (FBI).”

4) Murphy D, Gemmell B, Vaccari L, Li C, Bacosa H, Evans M, Gemmell C, Harvey T, Jalali M, Niepa THR. (2016) An in-depth survey of the oil spill literature since 1968: Long term trends and changes since Deepwater Horizon (Submitted).

5) Niepa THR, Vaccari L, Leheny R, Goulian M, Lee D, and Stebe K (2016). Films of Bacteria at Interfaces (FBI) formation: A dynamic response to interfacial stress (In preparation)

Doctoral Training–Advisor: Dacheng Ren, Biomedical and Chemical Engineering, Syracuse University

PHD. Thesis: Electrochemical Control of Bacterial Persister Cells

6) Szkotak R, Niepa THR, Jawrani N, Gilbert JL, Jones MB, Ren D. Differential Gene Expression to Investigate the Effects of Low-level Electrochemical Currents on Bacillus subtilis. AMB Express 1 (2011) 39.

7) Niepa THR, Gilbert JL, and Ren D. Controlling Pseudomonas aeruginosa persister cells by weak electrochemical currents and synergistic effects with tobramycin. Biomaterials 33(30) (2012) 7356-7365.

8) Niepa THR, Snepenger LM, Hao Wang, Sivan S, Gilbert JL, Jones MB, and Ren D (2016) Sensitizing Pseudomonas aeruginosa cells to antibiotics by electrochemical disruption of membrane functions. Biomaterials 74 (2016) 267-279.

9) Niepa THR, Hao Wang, Dabrowiak JC, Gilbert JL, and Ren D (2015) Synergy between tobramycin and trivalent chromium ion in electrochemical control of Pseudomonas aeruginosa. Acta Biomaterialia 36 (2016) 286–295.

10) Ren D., Zhang M., Niepa THR, and Gilbert J. (2014). Systems and Method for Controlling Bacterial Persister Cells with Weak Electric Currents. (Awarded Patent # 8 569 027).

11) Niepa THR, Wang H, Gilbert JL and Ren D. (2016) Electrochemical Control of Pseudomonas aeruginosa Persister and Biofilm Cells using TGON™ 805 in single and dual chamber systems (Submitted).

12) Niepa THR, Haveman G, Goyal P, and Ren D (2016) Electrochemical treatment of Pseudomonas aeruginosain a rabbit model of sinusitis (In preparation).

Teaching Interests:  My vision is to promote active learning among organized team of students and to develop new methods to help them identify emerging research topics and design new solutions from a multidisciplinary approach. Thus, I am looking forward to teaching the core courses (including Transport, Thermodynamics, Reaction Engineering, Separation Processes) and specialty Bioengineering courses such as Biomaterials, Fields, Forces, and Flows in Biological Systems, Biochemical Engineering or Bioelectrochemistry.

Teaching Experience: Over the course of my academic and professional training, I have participated in and contributed to various teaching and research training experiences. These inspired my pursuit of an academic career so that I can continue to support future generations of scholars, especially those from disadvantaged backgrounds. As a research assistant, my main involvement in teaching was through guest lecturing in the areas of biotechnology, medical devices, and entrepreneurship. Lectures were structured within the course framework as taught by a faculty member, or based on my area of expertise in microbial biofilms. My efforts were well-received by students and also effective as indicated by positive reviews in independent evaluations and students’ test performance. Another aspect of teaching entails training graduate and undergraduate students to acquire the research skills essential for their completion of their independent study. I helped four graduate and three undergraduate students to quickly become familiar with lab techniques and so independent researchers to contribute to the topic of bacterial electrophysiology. The success of my efforts led to co-authorship with two of my research mentees in scientific publications. Also as a doctoral student, my mentoring experiences reinforced my desire to become a faculty member. In the summers of 2012 and 2013, I coordinated the Syracuse University-Emerging Frontiers in Research and Innovation–Research Experience and Mentoring (EFRI–REM) program. I have pursued new mentoring opportunities during my fellowship at the University of Pennsylvania through the NSF Louis Stokes Alliance for Minority Participation (LSAMP) or through presentations at seminars and keynote addresses during STEM conferences. My commitment to engagement and teaching resulted in my receipt of the Appreciation Award for Dedication, Continuous Inspiration, and outstanding Contribution to Science and Engineering Studentsfrom the Greater Philadelphia LSAMP.

Entrepreneurship: I have professional experience from starting up a small business that has both enhanced my creativity and increased my understanding of the challenges of and opportunities for technology transfer. In 2011, I successfully transferred a basic scientific idea developed in the lab into a business idea. I co-founded Helios Innovative Technology, Inc. (now PurpleSun, Inc.), which develops automated sterilization devices to prevent bacterial cross-contamination and fight hospital-acquired infections.

Founder of Helios Innovative Technology (now PurpleSun); Funding: 2011 New York State Plan Business Competition ($60,000), Angel Investor ($500,000).

13) Romo L., Garritano N., Niepa THR.(2013). Door Handle Sterilization System, WO Patent 2,013,025,894. (Patent Application).

Future Directions: As faculty member, I will strengthen and grow my research efforts while developing new, effective teaching programs. The goal of my research efforts is to elucidate the physicochemical mechanisms regulating microbial growth in various environments and, based on this knowledge, design sustainable means to control bacteria. My previous research on the electrophysiology of highly drug-tolerant bacterial cells opens the door for new approaches to cure chronic infections. Building on this foundation, my planned translational-research program would target the design of alternate ways to diagnose and eradicate bacteria using conductive-substrate interfaces and medical devices. Another research area I will pursue is the development of soft nanomaterials for biotechnological applications such as drug release and identification. By developing the means for selective diffusion through functional membranes, I propose to control physiological responses of microbes and direct their metabolic activity towards desired ends e.g., creation of new materials and bioproducts. Thus, the development of the functional membrane would allow the creation of functional nanocultures to encapsulate probiotics or unculturable cells as well as upstream bioprocess technologies to facilitate high-throughput screening and characterization of bioactive molecules. Finally, I aim to elucidate the effects of interfacial properties of oil-water on the metabolic performance of bacteria in bioprocesses involving oil-water emulsions. I propose to characterize the mechanics and metabolic profiles of films of bacteria at interfaces subjected to strong interfacial energies, and elaborate on this understanding to model sustainability in bioremediation or prevent the biodeterioration of economically relevant products.

As a teacher, my vision is to promote active learning among organized team of students and to develop new methods to help them identify emerging research topics and design new solutions from a multidisciplinary approach. One of my goals as a faculty member is to translate my research ideas to medical and industrial technologies and encourage the development of an entrepreneurial spirit among my students so they are aware of this additional pathway through which research outcomes can benefit society.