Spencer Haws, Postdoctoral Research Fellow in the laboratory of Jennifer E. Phillips-Cremins, Associate Professor and Dean’s Faculty Fellow in Bioengineering and in Genetics, was awarded a 2022 Druckenmiller Fellowship from the New York Stem Cell Foundation Research Institute (NYSCF). This prestigious program is the largest dedicated stem cell fellowship program in the world and was developed to train and support young scientists working on groundbreaking research in the field of stem cell research. Haws is one of only five inductees into the 2022 class of fellows.
Haws earned his Ph.D. in Nutritional Sciences in 2021 from the University of Wisconsin-Madison, where he studied metabolism-chromatin connections under the mentorship of John Denu, Professor in Biomolecular Chemistry at the University of Wisconsin-Madison. As a NYSCF – Druckenmiller Fellow in the Cremins Laboratory for Genome Architecture and Spatial Neurobiology, Haws is using this previously developed expertise to frame his investigations into the underlying mechanisms driving the neurodegenerative disorder fragile X syndrome (FXS). “Ultimately, I hope that this work will help guide the development of future FXS-specific therapeutics of which none currently exist,” says Haws.
Cells in complex organisms undergo frequent changes, and researchers have struggled to monitor these changes and create a comprehensive profile for living cells and tissues. Historically researchers have been limited to only 3-5 markers due to spectral overlaps in fluorescence microscopy, an essential tool required for imaging cells. With only this small handful of markers, it is difficult to monitor protein expressions of live cells and a comprehensive profile of cellular dynamics cannot be created. However, a new study in Nature Biotechnology addresses these limitations by demonstrating a new method for comprehensive profiling of living cells.
Jina Ko, PhD
Jina Ko, Assistant Professor in Bioengineering in the School of Engineering and Applied Science and in Pathology and Laboratory Medicine in the Perelman School of Medicine, conducted postdoctoral research at Massachusetts General Hospital (MGH) and the Wyss Institute at Harvard University, and the work for this study was done under the supervision of Jonathan Carlson M.D., Ph.D. and Ralph Weissleder M.D., Ph.D. of MGH. Ko’s lab at Penn develops novel technologies using bioengineering, molecular biology, and chemistry to address diagnostic challenges for precision medicine.
To address these limitations in microscopy, the team developed a new chemistry tool which was highly gentle to cells. This “scission-accelerated fluorophore exchange (or SAFE)” method utilizes “click” chemistry, a type of chemistry that follows examples found in nature to create fast and simple reactions. This new SAFE method functions with non-toxic conditions to living cells and tissues, whereas previous methods have used harsh chemicals that would strip off fluorophores and consequently would not work with living cells and tissues.
With the development of SAFE, the authors demonstrated that researchers can now effectively perform multiple cycles of cell profiling and can monitor cellular changes over the course of their observations. Instead of the previous limitation of 3-5 markers total, SAFE allows for many more cycles and can keep track of almost as many markers as the researcher wants. One can now stain cells and quench/release fluorophores and repeat the cycle multiple times for multiplexing on living cells. Each cycle can profile 3 markers, and so someone interested in profiling 15 markers could easily perform 5 cycles to achieve this much more comprehensive cell profile. With this breakthrough in more detailed imaging of cells, SAFE demonstrates broad applicability for allowing researchers to better investigate the physiologic dynamics in living systems.
This study was supported by the Schmidt Science Fellows in Partnership with the Rhodes Trust and National Institutes of Health, National Cancer Institute (K99CA256353).
She joins 28 early-career scientists from around the world in this year’s cohort, with each receiving support for one to two years, $100,000 in salary support per year, individualized mentoring, and a series of professional development sessions as they pivot to the next stages of their research agendas.
The fellowship is a program of Schmidt Futures, the philanthropic initiative of Eric and Wendy Schmidt that aims to tackle society’s toughest challenges by supporting interdisciplinary researchers at the start of their careers.
“Our latest group of Schmidt Science Fellows embodies our vision for this Program at its inception five years ago,” says Eric Schmidt, co-founder of Schmidt Futures and former CEO and Chairman of Google. “We find the most talented next-generation leaders from around the world and back these impressive young adults with the resources and networks they need to realize their full potential while addressing some of the big scientific questions facing the world. Congratulations to the 2022 Schmidt Science Fellows, I am excited to see where your science takes you and what you will achieve.”
Working at the intersection of materials science, biology, and applied clinical research, Zlotnick’s postdoctoral work will involve developing advanced bioprinting techniques for regenerative medicine. Such advances are necessary to recreate the multi-cellular composition of orthopedic tissues, such as those found in the knee joint. Lab-grown tissue models can then be used to broaden our understanding of how degenerative diseases progress after injury, limit the need for animal models, and serve as a platform for therapeutic discovery.
A group of bacteriophages, viruses that infect bacteria, imaged using transmission electron microscopy. New research sheds light on how bacteria fight off these invaders without triggering an autoimmune response. (Image: ZEISS Microscopy, CC BY-NC-ND 2.0)
During the last few years, CRISPR has grabbed headlines for helping treat patients with conditions as varied as blindness and sickle cell disease. However, long before humans co-opted CRISPR to fight genetic disorders, bacteria were using CRISPR as an immune system to fight off viruses.
In bacteria, CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) works by stealing small pieces of DNA from infecting viruses and storing those chunks in the genes of the bacteria. These chunks of DNA, called spacers, are then copied to form little tags, which attach to proteins that float around until they find a matching piece of DNA. When they find a match, they recognize it as a virus and cut it up.
Now, a paper published in Current Biology by researchers from the University of Pennsylvania Department of Physics and Astronomy shows that the risk of autoimmunity plays a key role in shaping how CRISPR stores viral information, guiding how many spacers bacteria keep in their genes, and how long those spacers are.
Ideally, spacers should only match DNA belonging to the virus, but there is a small statistical chance that the spacer matches another chunk of DNA in the bacteria itself. That could spell death from an autoimmune response.
“The adaptive immune system in vertebrates can produce autoimmune disorders. They’re very serious and dangerous, but people hadn’t really considered that carefully for bacteria,” says Vijay Balasubramanian, principal investigator for the paper and the Cathy and Marc Lasry Professor of Physics in the School of Arts & Sciences.
Balancing this risk can put the bacteria in something of an evolutionary bind. Having more spacers means they can store more information and fend off more types of viruses, but it also increases the likelihood that one of the spacers might match the DNA in the bacteria and trigger an autoimmune response.
Vijay Balasubramanian is the Cathy and Marc Lasry Professor of Physics at the Department of Physics and Astronomy of the University of Pennsylvania, a visiting professor at Vrije Universiteit Brussel, and a member of the Penn Bioengineering Graduate Group.
The U.S. Food and Drug Administration has expanded its approval for Kymriah, a personalized cellular therapy developed at the Abramson Cancer Center, this time for the treatment of adults with relapsed/refractory follicular lymphoma who have received at least two lines of systemic therapy. “Patients with follicular lymphoma who relapse or don’t respond to treatment have a poor prognosis and may face a series of treatment options without a meaningful, lasting response,” said Stephen J. Schuster, the Robert and Margarita Louis-Dreyfus Professor in Chronic Lymphocytic Leukemia and Lymphoma in the Division of Hematology Oncology. It’s the third FDAapproval for the “living drug,” which was the first of its kind to be approved, in 2017, and remains the only CAR T cell therapy approved for both adult and pediatric patients.
“In just over a decade, we have moved from treating the very first patients with CAR T cell therapy and seeing them live healthy lives beyond cancer to having three FDA-approved uses of these living drugs which have helped thousands of patients across the globe,” said Carl June, MD, the Richard W. Vague Professor in Immunotherapy in the department of Pathology and Laboratory Medicine in Penn’s Perelman School of Medicine and director of the Center for Cellular Immunotherapies in the Abramson Cancer Center and director of the Parker Institute for Cancer Immunotherapy at Penn. “Today’s news is new fuel for our work to define the future of cell therapy and set new standards in harnessing the immune system to treat cancer.”
Research from June, a member of the Penn Bioengineering Graduate Group, led to the initial FDA approval for the CAR T therapy (sold by Novartis as Kymriah) for treating acute lymphoblastic leukemia (ALL), one of the most common childhood cancers.
César de la Fuente, Presidential Assistant Professor in Psychiatry, Bioengineering, Microbiology, and in Chemical and Biomolecular Engineering has been honored with a 2022 Young Investigator Award by the Royal Spanish Society of Chemistry (RSEQ) for his pioneering research efforts to combine the power of machines and biology to help prevent, detect, and treat infectious diseases.
Congratulations to the two Bioengineering students to receive 2022 National Science Foundation Graduate Research Fellowship Program (NSF GRFP) fellowships. The prestigious NSF GRFP program recognizes and supports outstanding graduate students in NSF-supported fields. The eighteen Penn 2022 honorees were selected from a highly-competitive pool of over 12,000 applications nationwide. Further information about the program can be found on the NSF website.
Gianna Therese Busch, PhD student, Bioengineering
Gianna is a member of the systems biology lab of Arjun Raj, Professor in Bioengineering and Genetics. Her research focuses on single-cell differences in cancer metabolism and drug resistance.
Shawn Kang, BSE/MSE, Bioengineering (’22)
Shawn conducted research in the BIOLines Lab of Dan Huh, Associate Professor in Bioengineering, where he worked to develop more physiologically relevant models of human health and disease by combining organs-on-a-chip and organoid technology.
The following Bioengineering students also received Honorable Mentions: Michael Steven DiStefano, PhD student Rohan Dipak Patel, PhD student Abraham Joseph Waldman, PhD student
In a course from Annenberg’s David Lydon-Staley, seven graduate students conducted single-participant experiments. This approach, what’s known as an “n of 1,” may better capture the nuances of a diverse population than randomized control trials can.
David Lydon-Staley is an assistant professor of communication and principal investigator of the Addiction, Health, & Adolescence Lab in the Annenberg School for Communication.
To prep for an upcoming course he was teaching, Penn researcher David Lydon-Staley decided to conduct an experiment: Might melatonin gummies—supplements touted to improve sleep—help him, as an individual, fall asleep faster?
For two weeks, he took two gummies on intervention nights and none on control nights. The point, however, wasn’t really to find out whether the gummies worked for him (which they didn’t), but rather to see how an experiment with a single participant played out, what’s known as an “n of 1.”
Randomized control experiments typically include hundreds or thousands of participants. Their aim is to show, on average, how the intervention being studied affects people in the treatment group. But often “there’s a failure to include women and members of minoritized racial and ethnic groups in those clinical trials,” says Lydon-Staley, an assistant professor in the Annenberg School for Communication. “The single-case approach says, instead of randomizing a lot of people, we’re going to take one person at a time and measure them intensively.”
In Lydon-Staley’s spring semester class, Diversity and the End of Average, seven graduate students conducted their own n-of-1 experiments—on themselves—testing whether dynamic stretching might improve basketball performance or whether yoga might decrease stress. One wanted to understand the effect of journaling on emotional clarity. They also learned about representation in science, plus which analytical approaches might best capture the nuance of a diverse population and individuals with many intersecting identities.
“It’s not just an ‘n of 1’ trying to do what the big studies are doing. It’s a different perspective,” says Lydon-Staley. “Though it’s just one person, you’re getting a much more thorough characterization of how they’re changing from moment to moment.”
The Solomon R. Pollack Award for Excellence in Graduate Bioengineering Research is given annually to the most deserving Bioengineering graduate students who have successfully completed research that is original and recognized as being at the forefront of their field. This year Penn Bioengineering recognizes the outstanding work of two graduate students in Bioengineering: Erin Berlew and Rhea Chitalia.
Erin Berlew, Ph.D. candidate in Bioengineering
Erin Berlew is a Ph.D. candidate in the lab of Brian Chow, Associate Professor in Bioengineering. She successfully defended her thesis, titled “Single-component optogenetic tools for cytoskeletal rearrangements,” in December 2021. In her research, she used the BcLOV4 optogenetic platform discovered/developed in the Chow lab to control RhoGTPase signaling. Erin earned a B.S. in Chemistry from Haverford College in 2015 and was an Americorps member with City Year Philadelphia from 2015-2016. “Erin is a world-class bioengineering with an uncommon record of productivity gained through her complementary expertise in molecular, cellular, and computational biology,” says Chow. “She embodies everything wonderful, both academically and culturally, about our graduate program and its distinguished history.” Erin’s hobbies outside the lab include spending time with family, reading mystery novels, enjoying Philadelphia, and crossword puzzles. In the future, she hopes to continue to teach for the BE department (she has already taught ENGR 105 and served as a TA for undergraduate and graduate courses) and to conduct further research at Penn.
Rhea Chitalia, Ph.D. candidate in Bioengineering
Rhea Chitalia is a Ph.D. candidate in Bioengineering and a member of the Computational Biomarker Imaging Group (CBIG), advised by Despina Kontos, Matthew J. Wilson Associate Professor of Research Radiology II in the Perelman School of Medicine. Rhea completed her B.S.E. in Biomedical Engineering at Duke University in 2015. Her doctoral research concerns leveraging machine learning, bioinformatics, and computer vision to develop computational imaging biomarkers for improved precision cancer care. In December 2021 she successfully defended her thesis titled “Computational imaging biomarkers for precision medicine: characterizing intratumor heterogeneity in breast cancer.” “It has been such a privilege to mentor Rhea on her dissertation research,” says Kontos. “Rhea has been a star graduate student. Her work has made fundamental contributions in developing computational methods that will allow us to gain important insight into tumor heterogeneity by utilizing a multi-modality imaging approach.” David Mankoff, Matthew J. Wilson Professor of Research Radiology in the Perelman School of Medicine, served as Rhea’s second thesis advisor. “It was a true pleasure for me to work with Rhea and to Chair her BE Thesis Committee,” Mankoff adds. “Rhea’s Ph.D. thesis and thesis presentation was one of the best I have had the chance to be involved with in my graduate mentoring career.” After graduation, Rhea hopes to further precision medicine initiatives through the use of real world, multi-omic data in translational industry settings. She will be joining Invicro as an Imaging Scientist. In her spare time, Rhea enjoys trying new restaurants, reading, and spending time with friends and family.
A suspension of particles of different sizes during shearing experiments conducted in the lab of Paulo Arratia, with arrows indicating particle “flow” and trajectories. In a new study published in Nature Physics, researchers detail the relationship between a disordered material’s individual particle arrangement and how it reacts to external stressors. The study also found that these materials have “memory” that can be used to predict how and when they will flow. (Image: Arratia lab)
New research published in Nature Physics details the relationship between a disordered material’s individual particle arrangement and how it reacts to external stressors. The study also found that these materials have “memory” that can be used to predict how and when they will flow. The study was led by Larry Galloway, a Ph.D. student in the lab of Paulo Arratia, and Xiaoguang Ma, a former postdoc in the lab of Arjun Yodh, in collaboration with researchers in the labs of Douglas Jerolmack and Celia Reina.
A disordered material is randomly arranged at the particle-scale, e.g. atoms or grains, instead of being systematically distributed—think of a pile of sand instead of a neatly stacked brick wall. Researchers in the Arratia lab are studying this class of materials as part of Penn’s Materials Research Science & Engineering Center, where one of the program’s focuses is on understanding the organization and proliferation of particle-scale rearrangements in disordered, amorphous materials.
The key question in this study was whether one could observe the structure of a disordered material and have some indication as to how stable it is or when it might begin to break apart. This is known as the yield point, or when the material “flows” and begins to move in response to external forces. “For example, if you look at the grains of a sand castle and how they are arranged, can I tell you whether the wind can blow it over or if it has to be hit hard to fall over?” says Arratia. “We want to know, just by looking at the way the particles are arranged, if we can say anything about the way they’re going to flow or if they are going to flow at all.”
While it has been known that individual particle distribution influences yield point, or flow, in disordered materials, it has been challenging to study this phenomenon since the field lacks ways to “quantify” disorder in such materials. To address this challenge, the researchers collaborated with colleagues from across campus to combine expertise across the fields of experimentation, theory, and simulations.
The authors are Larry Galloway, Erin Teich, Christoph Kammer, Ian Graham, Celia Reina, Douglas Jerolmack, Arjun Yodh, and Paulo Arratia from Penn; Xiaoguang Ma, previously a postdoc at Penn and now at the Southern University of Science and Technology in Shenzhen, China; and Nathan Keim, previously a postdoc at Penn and now at Pennsylvania State University.
Shawn Kang, BSE/MSE, Bioengineering (’22)
