BE Seminar: “Promoting Appendage/Limb Regeneration in Jellyfish, Drosophila, and Mouse” (Lea Goentoro)

We hope you will join us for our final seminar of the spring semester!

Speaker: Lea Goentoro, Ph.D.
Professor
Biology
California Institute of Technology

Date: Thursday, April 22, 2021
Time: 3:00-4:00 PM EDT
Zoom – check email for link or contact ksas@seas.upenn.edu

Abstract: Can limb regeneration be induced? In this talk, I will discuss our work to promote regeneration in animals with limited regeneration capacity. I will present our recent discovery of a strategy for inducing regenerative response in appendages, which works across three species that span the animal phylogeny. In Cnidaria, the frequency of appendage regeneration in the moon jellyfish Aurelia was increased by feeding with the amino acid L-leucine and the growth hormone insulin. In insects, the same strategy induced tibia regeneration in adult Drosophila. Finally, in mammals, L-leucine and sucrose administration induced digit regeneration in adult mice, including dramatically from mid-phalangeal amputation. The conserved effect of L-leucine and insulin/sugar suggests a key role for energetic parameters in regeneration induction. The simplicity by which nutrient supplementation can induce appendage regeneration provides a testable hypothesis across animals.

Lea Goentoro Bio: Lea Goentoro is a Professor of Biology in the Division of Biology and Biological Engineering at the California Institute of Technology. She holds a B.S. in Chemical Engineering from University of Wisconsin, Madison and a Ph.D. in Chemical Engineering from Princeton University. Prior to joining Caltech, she did postdoctoral training in the Department of Systems Biology at Harvard Medical School. Her work has been supported by the Damon-Runyon Cancer Foundation, the James S. McDonnell Foundation, the National Science Foundation, and the National Institute of Health.

Penn, CHOP and Yale Researchers’ Molecular Simulations Uncover How Kinase Mutations Lead to Cancer Progression

by Evan Lerner

A computer model of a mutated anaplastic lymphoma kinase (ALK), a known oncogenic driver in pediatric neuroblastoma.

Kinases are a class of enzymes that are responsible for transferring the main chemical energy source used by the body’s cells. As such, they play important roles in diverse cellular processes, including signaling, differentiation, proliferation and metabolism. But since they are so ubiquitous, mutated versions of kinases are frequently found in cancers. Many cancer treatments involve targeting these mutant kinases with specific inhibitors.

Understanding the exact genetic mutations that lead to these aberrant kinases can therefore be critical in predicting the progression of a given patient’s cancer and tailoring the appropriate response.

To achieve this understanding on a more fundamental level, a team of researchers from the University of Pennsylvania’s School of Engineering and Applied Science and Perelman School of Medicine, the Children’s Hospital of Philadelphia (CHOP) and researchers at the Yale School of Medicine’s Cancer Biology Institute, have constructed molecular simulations of a mutant kinase implicated in pediatric neuroblastoma, a childhood cancer impacting the central nervous system.

Using their computational model to study the relationship between single-point changes in the kinase’s underlying gene and the altered structure of the protein it ultimately produces, the researchers revealed useful commonalities in the mutations that result in tumor formation and growth. Their findings suggest that such computational approaches could outperform existing profiling methods for other cancers and lead to more personalized treatments.

The study, published in the Proceedings of the National Academy of Sciences, was led by Ravi Radhakrishnan, Professor and chair of Penn Engineering’s Department of Bioengineering and professor in its Department of Chemical and Biomolecular Engineering, and Mark A. Lemmon, Professor of Pharmacology at Yale and co-director of Yale’s Cancer Biology Institute. The study’s first authors were Keshav Patil, a graduate student in Penn Engineering’s Department of Chemical and Biomolecular Engineering, along with Earl Joseph Jordan and Jin H. Park, then members of the Graduate Group in Biochemistry and Molecular Biology in Penn’s Perelman School of Medicine. Krishna Suresh, an undergraduate student in Radhakrishnan’s lab, Courtney M. Smith, a graduate student in Lemmon’s lab, and Abigail A. Lemmon, an undergraduate in Lemmon’s lab, contributed to the study. They collaborated with Yaël P. Mossé, Associate Professor of Pediatrics at Penn Medicine and in the division of oncology at CHOP.

“Some cancers rely on the aberrant activation of a single gene product for tumor initiation and progression,” says Radhakrishnan. “This unique mutational signature may hold the key to understanding which patients suffer from aggressive forms of the disease or for whom a given therapeutic drug may yield short- or long-term benefits. Yet, outside of a few commonly occurring ‘hotspot’ mutations, experimental studies of clinically observed mutations are not commonly pursued.”

Read the full post in Penn Engineering Today.

Manuela Raimondi Appointed Visiting Professor in Bioengineering

Manuela Raimondi, PhD

Manuela Teresa Raimondi was appointed Visiting Professor in Bioengineering in the Associated Faculty of the School of Engineering and Applied Science for the 2020-2021 academic year. Raimondi received her Ph.D. in Bioengineering in 2000 from Politecnico di Milano, Italy. She is currently a Full Professor of Bioengineering at Politecnico di Milano in the Department of Chemistry, Materials and Chemical Engineering “G. Natta”, where she teaches the course “Technologies for Regenerative Medicine” in the Biomedical Engineering graduate program.

Raimondi is the founder and Director of the Mechanobiology Lab and of the Interdepartmental Live Cell Imaging lab. She has pioneered the development of cutting edge tools for cell modelling, ranging from micro-engineered stem cell niches, to miniaturized windows for in vivo intravital imaging, to microfluidic culture systems to engineer tissue-equivalents and organoids for cell modelling and drug discovery. Her platforms are currently commercialized by her start-up, MOAB srl. Her research is funded by the European Research Council (ERC), by The National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), by the European Commission, and by the European Space Agency.

“Getting to Penn was quite the challenge with the various travel restrictions and the pandemic, but I am used to overcoming adverse odds and I am really excited to be here now,” says Dr. Raimondi. “In this challenging time, when many new barriers are coming up, I think building bridges and new scientific collaborations is even more important. I very much look forward to being part of the Penn research community.”

Dr. Raimondi with host Riccardo Gottardi, PhD on Smith Walk

During her sabbatical at Penn, Raimondi is investigating her hypothesis that stem cells pluripotency reprogramming can be guided by mechanical cues. Over the past five years, she has cultured many different stem cell types in the “Nichoids,” the synthetic stem cell niche she developed, and gathered robust evidence on how physical constraints at the microscale level upregulate pluripotency. Raimondi is hosted in the Bioengineering and Biomaterials Lab of Riccardo Gottardi, Assistant Professor in Bioengineering and in Pediatrics at the Perelman School of Medicine, where she is helping to refine human stem cell sources that could be minimally manipulated for translational tissue engineering for a safe and effective use in regenerative therapies, as a key issue for clinical translation is the maintenance or enhancement of multipotency during cell expansion without exogenous agents or genetic modification.

“Dr. Raimondi is a trailblazer in Italy in regenerative medicine who has introduced many new concepts in a sometimes musty academic environment and has shattered a number of glass ceilings,” says Dr. Gottardi. “I think her sabbatical at Penn is a great opportunity for her and for the Penn community to build new and exciting trans-Atlantic collaborations.”

César de la Fuente on AIChE’s 35 Under 35 List

César de la Fuente, PhD

César de la Fuente, Presidential Assistant Professor in Psychiatry, Microbiology, and Bioengineering, was named one of the American Institute of Chemical Engineers’ (AIChE) 35 members under 35 for 2020.

“The AIChE 35 Under 35 Award was founded to recognize young chemical engineers who have achieved greatness in their fields,” reads the 2020 award announcement. “The winners are a group of driven, engaged, and socially active professionals, representing the breadth and diversity that chemical engineering exemplifies.”

De la Fuente was named in the list’s “Bioengineering” category for his his lab’s work in machine biology. Their goal is to develop computer-made tools and medicines that will combat antibiotic resistance. De la Fuente has already been featured on several other young innovators lists, including MIT Technology Review’s 35 under 35 and GEN’s Top 10 under 40, both in 2019. His research in antibiotic resistance has been profiled in Penn Today and Penn Engineering Today, and he was recently awarded Penn Health-Tech’s inaugural NEMO Prize for his proposal to develop paper-based COVID diagnostic system that could capture viral particles on a person’s breath.

In addition to being named on the 2020 list, the honorees will receive a $500 prize and will be celebrated at the 2020 AIChE Annual Meeting this November.

Learn more about de la Fuente’s pioneering research on his lab website.

BE Seminar: “Predicting the Effects of Engineering Immune Cells Using Systems Biology Modeling” (Stacey Finley, USC)

The Penn Bioengineering virtual seminar series continues on October 1st.

Stacey Finley, PhD

 

Speaker: Stacey Finley, Ph.D.
Gordon S. Marshall Early Career Chair and Associate Professor of Biomedical Engineering and Biological Sciences
University of Southern California

 

Date: Thursday, October 1, 2020
Time: 3:00-4:00 pm
Zoom – check email for link or contact ksas@seas.upenn.edu

Title: “Predicting the Effects of Engineering Immune Cells Using Systems Biology Modeling”

Abstract:

Systems biology approaches, including computational models, provide a framework to test biological hypotheses and optimize effective therapeutic strategies to treat human diseases. In this talk, I present recent work in modeling signaling in cancer-targeting immune cells, including CAR T cells at Natural Killer cells. Chimeric antigen receptors (CARs) are comprised of a variety of different activating domains and co-stimulatory domains that initiate signaling required for T cell activation. There is a lack of understanding of the mechanisms by which activation occurs. We apply mathematical modeling to investigate how CAR structure influences downstream T cell signaling and develop new hypotheses for the optimal design of CAR-engineered T cell systems. Natural Killer cells also provide a useful platform for targeting cancer cells. However, NK cells have been shown to exhibit reduced killing ability with prolonged stimulation by cancer cells. We use a combination of mechanistic model, optimal control theory and in silico synthetic biology to investigate strategies to enhance NK cell-mediated killing.

Bio:

Stacey D. Finley is the Gordon S. Marshall Early Career Chair and Associate Professor of Biomedical Engineering at the University of Southern California. Dr. Finley received her B.S. in Chemical Engineering from Florida A & M University and obtained her Ph.D. in Chemical Engineering from Northwestern University. She completed postdoctoral training at Johns Hopkins University in the Department of Biomedical Engineering. Dr. Finley joined the faculty at USC in 2013, and she leads the Computational Systems Biology Laboratory. Dr. Finley has joint appointments in the Departments of Chemical Engineering and Materials Science and Biological Science, and she is a member of the USC Norris Comprehensive Cancer Center. Dr. Finley is also the Director of the Center for Computational Modeling of Cancer at USC. Her research is supported by grants from NSF, NIH, and the American Cancer Society.

Selected honors: 2016 NSF Faculty Early CAREER Award; 2016 Young Innovator by the Cellular and Molecular Bioengineering journal; Leah Edelstein-Keshet Prize from the Society of Mathematical Biology; Junior Research Award from the USC Viterbi School of Engineering; the Hanna Reisler Mentorship Award; 2018 AACR NextGen Star; 2018 Orange County Engineering Council Outstanding Young Engineer

See the full list of upcoming Penn Bioengineering fall seminars here.

BE Seminar: “Stem Cell Fate is a Touchy Subject” (Quinton Smith, MIT)

The first lecture in the Fall 2020 Penn Bioengineering Seminar Series will be held Thursday, September 10th. All seminars this semester will be held virtually on Zoom.

Quinton Smith, PhD

Speaker: Quinton Smith, Ph.D.
Postdoctoral Fellow
Laboratory for Multiscale Regenerative Technologies
Massachusetts Institute of Technology

Date: Thursday, September 10, 2020
Time: 3:00-4:00 pm
Zoom – check email for link or contact ksas@seas.upenn.edu

Title: “Stem Cell Fate is a Touchy Subject”

Abstract:

The success of regenerative cell therapy relies on the integration of a functional vascular system within the redeveloping tissue, to mediate the exchange of oxygen, nutrients and waste. Although the advent of human induced pluripotent stem cells (hiPSCs) has accelerated progress towards this goal, owing to their potential to generate clinically relevant scales of patient-specific cells, techniques to drive their specification mainly rely on chemical cues. In this seminar, I will discuss engineering strategies to control the complex stem cell extracellular milieu, emphasizing the importance of mechanical cues during hiPSC development, specification and downstream functionality as it relates to vascular differentiation.

Bio:

Quinton Smith received his PhD in Chemical and Biomolecular Engineering from Johns Hopkins University in 2017 after completing his bachelor’s degree in Chemical Engineering from the University of New Mexico. As a graduate student under the guidance of Dr. Sharon Gerecht, Quinton implemented various engineering tools to explore the roles of physical and chemical cues on stem cell lineage specification and downstream maturation. Dr. Smith is currently a postdoctoral fellow under the mentorship of Dr. Sangeeta Bhatia at MIT’s Koch Institute for Integrative Cancer Research, where he is investigating the role biliary epithelium in liver regeneration. Dr. Smith’s predoctoral work was supported by an NIH/NHLBI F-31 and NSF Graduate Research Fellowship. He is a recipient of the 2017 Siebel Scholar award, and most recently joined the class of 2018 HHMI Hanna Gray Fellows.

See the full list of upcoming Penn Bioengineering fall seminars here.

Getting Physical with Developmental Biology Research

macrophages Discher
Dennis Discher, Ph.D.

By Izzy Lopez

While genetics and biochemistry research has dominated the conversation about how human bodies are formed, new research — with an old twist — is proposing that there is another star in the show of human development: mechanical forces.

At the turn of the twentieth century, medical research relied on simple mechanics to explain scientific phenomena, including how human cells morph into shape from embryo to newborn and beyond. As better chemistry techniques and DNA research burst onto the scene, however, the idea that cells could be affected by physical forces took a back seat. Now researchers are referring back to this vintage idea and bringing it into the 21st century.

Dennis Discher, Robert D. Bent Professor in the Departments of Chemical and Biomolecular Engineering, Bioengineering and Mechanical Engineering and Applied Mechanics, was featured in a recent article in Knowable Magazine for his research on the human heart and how mechanical forces exerted on heart cells give the vital organ its necessary stiffness during development.

Read the full story on the Penn Engineering blog.