News

2018-04-19

Emily Chen was selected as one of the Mavis Future Faculty Fellows (MF3) for the 2018-2019 academic year. This program is designed to facilitate the training for the next generation of great engineering professors.

Engineering at Illinois is internationally recognized for the impact of our research and the strength of our graduate education. The doctoral programs that produce this reputation are primarily research-focused and may not provide students interested in academic careers with the opportunity to gain the knowledge of how to become a highly productive faculty member.

To help address this issue, the Office of Engineering Graduate, Professional and Online Programs facilitates the MF3 Academy where fellows participate in a series of workshops, seminars, and activities that cover various aspects of an academic career. Workshop themes include describing life as a faculty member, writing cover letters and CVs, preparing for campus interviews, and defining and achieving success as a faculty member. These workshops are available to all engineering graduate students.

The three main components to the MF3 Academy are research, teaching and mentoring. All fellows will become proficient in these core areas through various activities and events. The activities in each area will be designed to enhance the graduate students’ experiences in their departments. In addition, the fellows will complete a capstone experience that will enhance their professional development in a self-directed area.

Learn more about MF3

2018-04-17

The TiMe Cohort hosted the second-annual Tissue Microenvironment (TiMe) Day Symposium and Poster Session on April 13, 2018 at the Beckman Institute for Advanced Science and Technology. There were over seventy attendees from 14 departments across campus including guests from industry. The symposium explored different aspects of the tissue microenvironment through six faculty research talks: two by keynote speakers Drs. Steven Altschuler and Lani Wu from UCSF; three plenary talks by Illinois faculty: Drs. Erik Nelson, Stephen Boppart, and Jefferson Chan; and one by External Advisory Board Member Dr. Chandrajit Bajaj from UT Austin. Hailey Knox, Sisi He, Sushant Bangru, and Whitney Sinclair gave graduate student rapid talks to conclude the research portion of the symposium. The poster session and competition had an impressive twenty-four participants and Drs. Thomas Gaj and Shannon Sirk were tasked with selecting the top posters. The competition was so fierce that they were unable to choose only three winners, and so the day closed with four: Hailey Knox, Liqian Ma, Phuong Le, and Whitney Sinclair.
Acknowledgements

Deepest gratitude goes to the faculty speakers from across the country who came to support the TiMe Symposium and program. The Keynote guest faculty speakers from the University of California, San Francisco Drs. Lani Wu and Steven Altschuler. Dr. Altschuler and Dr. Wu spoke about tissue patterning and dysregulation in gut epithelium and the proliferation-senescence cell fate decision. Illinois faculty provided additional discussions about the tissue microenvironment with plenary talks by Dr. Erik Nelson –“Cholesterol, its Metabolites and the Tumor Microenvironment”, Dr. Stephen Boppart –“Shedding Light on the Dynamic Tumor Microenvironment”, and Dr. Jefferson Chan –“Development of Photoacoustic Probes for Non-invasive Imaging of Tissue Environments.” Dr. Chandrajit Bajaj from the University of Texas at Austin and an External Advisory Board member spoke about his research on infrared imaging “The Promise of Machine Learning for Infrared Spectroscopy”. Dr. Peter So from MIT and Dr. Bruce Wheeler from University of California, San Diego – both External Advisory Board members – provided additional support, questions, and comments throughout the event. Dr. Thomas Gaj and Dr. Shannon Sirk had the nearly impossible challenge of listening to, ranking, and deliberating on 24 posters from graduate students and postdoctoral fellows from across campus.

The event would not have been possible without the time and dedication of the TiMe cohort and administrative team. Emily Chen and Jan Lumibao were the masterminds behind organizing the symposium and made the day seamless. Sisi He, Jamila Hedhli, Clare Ko, Seth Kenkel, Joanne Li, Phuong Le, and Ruibo Wang sent out symposium communications across campus, encouraged colleagues to present and attend, and are now tasked with selecting the next cohort of Tissue Microenvironment trainees. Drs. Rohit Bhargava and Rex Gaskins are ever the guiding hands for the program and Krista Smith and Paloma Pearson keep the program advancing daily.

The event was sponsored by NIH T32 Award T32EB019944, the Cancer Center at Illinois, and the Beckman Institute with additional support from the College of Engineering, Carl R. Woese Institute for Genomic Biology, and the Department of Materials Science. An additional thanks to the Cancer Center at Illinois for providing the award money for the poster session.

2018-04-06

Sisi He was selected for an oral presentation at ENDO 2018. She was awarded Endocrine Society Outstanding Abstract Award & EndoCareers Early Career Forum Travel Award.

Abstract:
The poor prognosis of ovarian cancer patients (5-year survival is less than 50%) is due, in part, to progressive development of resistance to chemotherapy. Overexpression of the difficult to target protein, multidrug resistance protein 1 (MDR1)/P-glycoprotein, is a common resistance mechanism. We describe BHPI, a novel estrogen receptor α (ERα) biomodulator that inactivates MDR1 and restores sensitivity of highly resistant ovarian cancer cells to therapeutically relevant concentrations of taxanes. 30-70% of ovarian tumors are ERα+, but antiestrogens are usually ineffective. BHPI is a first-in-class non-competitive ERα biomodulator that strongly inhibits proliferation of anchorage-dependent and anchorage-independent, antiestrogen-resistant, ERα positive ovarian cancer cells (CaOV-3 and PEO4). BHPI works by distorting a recently unveiled signaling pathway, in which estrogen-ERα elicits a rapid, moderate, and transient “anticipatory” activation of the endoplasmic reticulum (EnR) stress sensor, the unfolded protein response (UPR). BHPI, acting via ERα, elicits sustained hyperactivation of the UPR, converting it from cytoprotective to cytotoxic. BHPI-ERα strongly activates plasma membrane phospholipase C γ (PLCγ). The activated PLCγ produces inositol triphosphate (IP3), which bind to and open EnR IP3 receptors (IP3R) resulting in rapid efflux of Ca2+ stored in EnR lumen into the cytosol. This strongly activates the UPR. To restore normal calcium homeostasis, powerful ATP-dependent EnR SERCA Ca2+ pumps, which pump Ca2+ from cytosol into the EnR, are activated. Because the EnR Ca2+ IP3R channels are open, the Ca2+pumped into the EnR leaks back out, leading to an ATP-depleting futile cycle. Reducing intracellular ATP with BHPI nearly abolishes MDR1-mediated efflux in multidrug resistant OVCAR-3 ovarian cancer cells. BHPI increased sensitivity of the highly multidrug resistant OVCAR-3 cells to killing by paclitaxel by more than a thousand fold. BHPI was also effective in other multidrug resistance models. Studies evaluating the ability of BHPI to restore sensitivity to taxanes in physiologically relevant models are underway. Because the UPR is nearly inactive in most normal cells and is overexpressed in ERα+ breast and ovarian tumors, this represents an innovative strategy for selectively targeting multidrug resistance in ovarian cancer and breast cancer.

2018-04-06

Authors:

Ruibo Wang, Kaimin Cai, Hua Wang, Chen Yin and Jianjun Cheng

Abstract:

In this work, we report selection of covalent linker on anomeric position of N-azidoacetylmannosamine (ManNAz) for caging its metabolic process. We synthesized DT-diaphorase responsive metabolic precursor HQ-NN-AAM using the optimized linker. The caged metabolite showed responsiveness to DT-diaphorase in vitro, resulting in metabolic incorporation of azido sugar on cell surface in multiple cell lines.

2018-03-08

Authors: Jee-Wei Emily Chen, Jan Lumibao, Audrey Blazek, H. Rex Gaskins and Brendan Harley*
Abstract:

Glioblastoma (GBM) is the most common, aggressive, and deadly form of adult brain cancer, and is associated with a short survival rate (median 12–15 months, 5+ year less than 5%). The complex tumor microenvironment includes matrix transitions at the tumor margin, such as gradations in hyaluronic acid (HA). In addition, metabolic stress induced by decreased oxygen content across the tumor may contribute to tumor progression. However, cross-talk between matrix composition and metabolic stress remains unclear. In this study, we fabricated an in vitro brain memetic HA-decorated gelatin hydrogel platform incorporating variable oxygen concentrations to mimic intra-tumoral hypoxia. We observed that EGFR status (wildtype vs. a constitutively active EGFRvIII mutant) of U87 GBM cells affected proliferation and metabolic activity in response to hypoxia and matrix-bound HA. The use of an invasion assay revealed that invasion was significantly enhanced in both cell types under hypoxia. Moreover, we observed compensatory secretion of soluble HA in cases of enhanced GBM cell invasion, consistent with our previous findings using other GBM cell lines. Interestingly, U87 GBM cells adapted to hypoxia by shifting toward a more anaerobic metabolic state, a mechanism that may contribute to GBM cell invasion. Collectively, these data demonstrate that the use of a three-dimensional hydrogel provides a robust method to study the impact of matrix composition and metabolic challenges on GBM cell invasion, a key factor contributing to the most common, aggressive, and deadly form of adult brain cancer.

Originally published on 2018-02-22

The Tissue Microenvironment class was privileged to spend an hour and a half talking with Dr. Oguzhan Alagoz from the University of Wisconsin-Madison. Dr. Alagoz came in from Wisconsin to speak to the ISE Graduate Seminar students, but graciously took time out to speak to the TiMe students about his experience in data informatics. Dr. Alagoz discussed his work on developing a mammography screening schedule for different populations based on prior screening history and personal risk characteristics of women. Although data analysis and tissue engineering seem far removed, students were able to ask about the specific markers the screening looked at as well as how engineering and the hospital setting can be intertwined.

Dr. Oguzhan Alagoz is a Professor of Industrial and Systems Engineering at the University of Wisconsin-Madison. He is also a professor at the Department of Population Health Sciences and serves as the director of NIH-funded Institute for Clinical and Translational Research (ICTR)-Simulation Center as well as the associated director for Wisconsin Institute for Healthcare Systems Engineering (WIHSE). The TiMe group thanks him for his time, questions, and imparted wisdom!

2017-11-09

Joanne Li, one of our Tissue Microenvironment students, recently published a paper on topically treating diabetic wounds with microscopy. Read the full paper here and see the abstract below.

Impaired skin wound healing is a significant comorbid condition of diabetes that is caused by poor microcirculation, among other factors. Studies have shown that angiogenesis, a critical step in the wound healing process in diabetic wounds, can be promoted under hypoxia. In this study, an angiogenesis-promoting topical treatment for diabetic wounds, which promotes angiogenesis by mimicking a hypoxic environment via inhibition of prolyl hydroxylase resulting in elevation or maintenance of hypoxia-inducible factor, was investigated utilizing a custom-built multimodal microscopy system equipped with phase-variance optical coherence tomography (PV-OCT) and fluorescence lifetime imaging microscopy (FLIM). PV-OCT was used to track the regeneration of the microvasculature network, and FLIM was used to assess the in vivo metabolic response of mouse epidermal keratinocytes to the treatment during healing. Results show a significant decrease in the fluorescence lifetime of intracellular reduced nicotinamide adenine dinucleotide, suggesting a hypoxic-like environment in the wounded skin, followed by a quantitative increase in blood vessel density assessed by PV-OCT. Insights gained in these studies could lead to new endpoints for evaluation of the efficacy and healing mechanisms of wound-healing drugs in a setting where delayed healing does not permit available methods for evaluation to take place.

2017-10-16

Sisi He and Dr. Erik Nelson recently published a paper on estrogen receptors.

Abstract: Estrogen receptors (ERs) mediate the actions of the steroidal estrogens, and are important for the regulation of several physiological and pathophysiological processes, including reproduction, bone physiology, cardiovascular physiology and breast cancer. The unique pharmacology of the ERs allows for certain ligands, such as tamoxifen, to elicit tissue- and context-specific responses, ligands now referred to as selective estrogen receptor modulators (SERMs). Recently, the cholesterol metabolite 27-hydroxychoelsterol (27HC) has been defined as an endogenous SERM, with activities in atherosclerosis, osteoporosis, breast and prostate cancers, and neural degenerative diseases. Since 27HC concentrations closely mirror those of cholesterol, it is possible that 27HC mediates many of the biological effects of cholesterol. This paper provides an overview of ER pharmacology and summarizes the work to date implicating 27HC in various diseases. Wherever possible, we highlight clinical data in support of a role for 27HC in the diseases discussed.

Orignally published on: 2017-05-18

Our inaugural Tissue Microenvironment (TiMe) Training Program Symposium hosted on Monday, May 15, 2107 was a great success! Each of the TiMe students presented a summary of their research projects, followed by presentations from members of the External Advisory Board, Dr. David Beebe (University of Wisconsin Madison), Dr. Peter So (MIT), and Dr. Bruce Wheeler (UCSD), and faculty preceptor Kris Kilian (UIUC).

We would like to thank all those who participated in the TiMe Poster Competition and congratulate the winners: Grand Prize – Sixian You; Runners-up: Shachi Mittal and Joanne Li.

Winners (left to Right): Sixian You, Joanne Li, Shachi Mittal

We also thank our primary sponsors: NIH T32 Award T32EB019944, Cancer Community at Illinois, and the Beckman Institute for making the event a success. Additional thanks goes to the Interdisciplinary Health Sciences Initiative (IHSI), College of Engineering, Carl R. Woese Institute for Genomic Biology, and the Department of Materials Science and Engineering.

Orignally published on 2017-05-18

Our inaugural Tissue Microenvironment (TiMe) Training Program Symposium hosted on Monday, May 15, 2107 was a great success! Each of the TiMe students presented a summary of their research projects, followed by presentations from members of the External Advisory Board, Dr. David Beebe (University of Wisconsin Madison), Dr. Peter So (MIT), and Dr. Bruce Wheeler (UCSD), and faculty preceptor Kris Kilian (UIUC).

We would like to thank all those who participated in the TiMe Poster Competition and congratulate the winners: Grand Prize – Sixian You; Runners-up: Shachi Mittal and Joanne Li.

We also thank our primary sponsors: NIH T32 Award T32EB019944, Cancer Community at Illinois, and the Beckman Institute for making the event a success. Additional thanks goes to the Interdisciplinary Health Sciences Initiative (IHSI), College of Engineering, Carl R. Woese Institute for Genomic Biology, and the Department of Materials Science and Engineering.

Read More: https://blogs.illinois.edu/view/7153/502358