Why New Cancer Treatments are Proliferating

by Karen L. Brooks

Doctors performing surgery.
Image: Penn Medicine News

In the five years since the FDA’s initial approval of chimeric antigen receptor (CAR) T cell therapy, Penn Medicine has gleaned 20 additional approvals related to drugs and techniques to treat or detect cancer.

Rather than being the single disease class many people refer to, “cancer” is a blanket term that covers more than 100 distinct diseases, many of which have little in common aside from originating with rapidly dividing cells. Since different cancers demand different treatments, it follows that any given new therapy emerging from any institution would be likely to be a new cancer treatment.

But why so many in just this five-year period?

The volume of new cancer treatments makes sense, says Abramson Cancer Center (ACC) director Robert Vonderheide, attributing the flurry of new cancer drug approvals to a recent “explosion” in knowledge about cancer biology.

“Much of that knowledge is about the immune system’s ability to attack cancer, which people seriously doubted until about 20 years ago. As soon as we had a clinical validation for this Achilles heel in cancer, the dam burst for ideas about other ways to exploit that vulnerability to come forward,” he says. “The first drug that came out to activate the immune system inspired the rest of the field to find the next drug, and the one after that. We as a field have moved from serendipity and empiricism to science-driven drug design.”

The first CAR T cell therapy approval invigorated Penn faculty interested in finding new ways to harness the immune system to fight cancer.

“An approval like that makes what you’re working on more of a reality,” says Avery Posey, an assistant professor of systems pharmacology and translational therapeutics in the Perelman School of Medicine, whose lab team spends much of its time trying to identify more specific antigens for solid tumors and also studies ways to optimize engineered donor T cells. “It brings a new perspective, showing that your work is more than basic research and can actually become drugs that impact patients’ lives. That’s a real motivator to keep pushing forward.”

Honing new immunotherapies is a priority among Penn researchers, but not every recently approved new cancer treatment or detection tool developed at the institution engages the immune system. Faculty have explored and introduced widely varying approaches to improving the standard of care for cancer patients.

Read the full story in Penn Medicine Magazine.

Avery Posey is a member of the Penn Bioengineering Graduate Group. Read more stories featuring Posey here.

Cesar de la Fuente On the “Next Frontier” of Antibiotics

César de la Fuente
César de la Fuente

In a recent CNN feature, César de la Fuente, Presidential Assistant Professor in Bioengineering, Psychiatry, Microbiology, and in Chemical and Biomolecular Engineering commented on a study about a new type of antibiotic that was discovered with artificial intelligence:

“I think AI, as we’ve seen, can be applied successfully in many domains, and I think drug discovery is sort of the next frontier.”

The de la Fuente lab uses machine learning and biology to help prevent, detect, and treat infectious diseases, and is pioneering the research and discovery of new antibiotics.

Read “A new antibiotic, discovered with artificial intelligence, may defeat a dangerous superbug” in CNN Health.

Mustafa Mir Named HHMI Freeman Hrabowski Scholar

Mustafa Mir

Mustafa Mir, Assistant Professor of Cell and Developmental Biology in the Perelman School of Medicine and member of the Penn Bioengineering Graduate Group, was selected as one of Howard Hughes Medical Institute’s 31 new Freeman Hrabowski Scholars. The group consists of outstanding early career faculty in science who have potential to become leaders in their research fields and to create diverse and inclusive lab environments in which everyone can thrive. Mir and his lab develop and apply new microscopes to directly visualize the molecular scale events that underlie gene expression within live embryos.

Read a Q&A with Mir in the Children’s Hopsital of Philadelphia (CHOP)’s Cornerstone Blog: “New Technologies Lead to New Discoveries’: Q&A With HHMI Scholar Mustafa Mir, PhD.

This announcement originally appeared in Penn Medicine News.

Penn Bioengineering Graduate Student on T Cell Therapy Improvements

Image: Courtesy of Penn Medicine News

 Neil Sheppard,  Adjunct Associate Professor of Pathology and Laboratory Medicine in the Perelman School of Medicine, and David Mai, a Bioengineering graduate student in the School of Engineering and Applied Science, explained the findings of their recent study, which offered a potential strategy to improve T cell therapy in solid tumors, to the European biotech news website Labiotech.

Mai is a graduate student in the lab of Carl H. June, the Richard W. Vague Professor in Immunotherapy in Penn Medicine, Director of the Center for Cellular Immunotherapies (CCI) at the Abramson Cancer Center, and member of the Penn Bioengineering Graduate Group.

Read “Immunotherapy in the fight against solid tumors” in Labiotech.

Read more about this collaborative study here.

Folding@Home: How You, and Your Computer, Can Play Scientist

by

Greg Bowman kneels, working on a server.
Folding@home is led by Gregory Bowman, a Penn Integrates Knowledge Professor who has appointments in the Departments of Biochemistry and Biophysics in the Perelman School of Medicine and the Department of Bioengineering in the School of Engineering and Applied Science. (Image: Courtesy of Penn Medicine News)

Two heads are better than one. The ethos behind the scientific research project Folding@home is that same idea, multiplied: 50,000 computers are better than one.

Folding@home is a distributed computing project which is used to simulate protein folding, or how protein molecules assemble themselves into 3-D shapes. Research into protein folding allows scientists to better understand how these molecules function or malfunction inside the human body. Often, mutations in proteins influence the progression of many diseases like Alzheimer’s disease, cancer, and even COVID-19.

Penn is home to both the computer brains and human minds behind the Folding@home project which, with its network, forms the largest supercomputer in the world. All of that computing power continually works together to answer scientific questions such as what areas of specific protein implicated in Parkinson’s disease may be susceptible to medication or other treatment.

Led by Gregory Bowman, a Penn Integrates Knowledge professor of Biochemistry and Biophysics in the Perelman School of Medicine who has joint appointments in the Department of Biochemistry and Biophysics in the Perelman School of Medicine and the Department of Bioengineering in the School of Engineering and Applied Science, Folding@home is open for any individual around the world to participate in and essentially volunteer their computer to join a huge network of computers and do research.

Using the network hub at Penn, Bowman and his team assign experiments to each individual computer which communicates with other computers and feeds info back to Philly. To date, the network is comprised of more than 50,000 computers spread across the world.

“What we do is like drawing a map,” said Bowman, explaining how the networked computers work together in a type of system that experts call Markov state models. “Each computer is like a driver visiting different places and reporting back info on those locations so we can get a sense of the landscape.”

Individuals can participate by signing up and then installing software to their standard personal desktop or laptop. Participants can direct the software to run in the background and limit it to a certain percentage of processing power or have the software run only when the computer is idle.

When the software is at work, it’s conducting unique experiments designed and assigned by Bowman and his team back at Penn. Users can play scientist and watch the results of simulations and monitor the data in real time, or they can simply let their computer do the work while they go about their lives.

Read the full story at Penn Medicine News.

Two from Penn Bioengineering Graduate Group Elected to the National Academy of Sciences

Four faculty from the University of Pennsylvania have been elected to the United States National Academy of Sciences (NAS). They are David Brainard of the School of Arts & Sciences; Duncan Watts of the Annenberg School of Communication, School of Engineering and Applied Science, and Wharton School; and Susan R. Weiss and Kenneth S. Zaret of the Perelman School of Medicine.

They join 120 members and 23 international members elected by their peers this year to NAS. Recognized for “distinguished and continuing achievements in original research,” this new class brings the total number of active members to 2,565 and of international members to 526.

Brainard and Zaret are members of the Penn Bioengineering Graduate Group.

David Brainard is the RRL Professor of Psychology, director of the Vision Research Center, and associate dean for the natural sciences in the School of Arts & Sciences. His research focuses on human vision, using both experiments and computer modeling of visual processing, to understand how the visual system deciphers information about objects from light entering the eye. Specifically, he and his lab are interested in color vision, conducting psychophysical experiments to investigate how the appearance of color is affected by an object’s surface properties and ambient light, and how color perception aids in identifying objects. Brainard is the recipient of many honors, including the Macbeth Award from the Inter-Society Color Council, Stein Innovation Award from Research to Prevent Blindness, and Edgard D. Tillyer Award from Optica. He is an elected member of the Society of Experimental Psychologists, a Silver Fellow of the Association for Research in Vision and Ophthalmology, and a Fellow of the Association for Psychological Science.

Kenneth Zaret

Kenneth S. Zaret is the Joseph Leidy Professor in the Department of Cell and Developmental Biology at the Perelman School of Medicine, director of the Institute for Regenerative Medicine, and a member of the Cell and Molecular Biology Graduate Program. His research focuses on gene regulation, cell differentiation, and chromatin structure, with a goal of elucidating these phenomena in the context of embryonic development and tissue regeneration. Pinpointing these aspects of development at the cellular level can serve as the basis for developing future therapeutics and experimental models that further scientists’ ability to understand and cure disease. Zaret has been the recipient of many honors, including a MERIT Award from the National Institutes of Health, the Stanley N. Cohen Biomedical Research Award, and election as a fellow of the American Association for the Advancement of Science.

Read the full announcement in Penn Today.

CiPD Fellows Recognized with Research Awards

Members of the inaugural cohort of fellows in the Center for Innovation and Precision Dentistry (CiPD)’s NIDCR T90/R90 Postdoctoral Training Program have been recognized for their research activities with fellows receiving awards from the American Association for Dental, Oral, and Craniofacial Research (AADOCR), the Society for Biomaterials, and the Osteology Foundation. All four of the honored postdocs are affiliated with Penn Bioengineering.

Zhi Ren

Zhi Ren won first place in the Fives-Taylor Award at the AADOCR Mini Symposium for Young Investigators. A postdoctoral fellow in the labs of Dr. Hyun (Michel) Koo at Penn Dental Medicine (and member of the Penn Bioengineering Graduate Group) and Dr. Kathleen Stebe of Penn Engineering, Dr. Ren’s research focuses on understanding how bacterial and fungal pathogens interact in the oral cavity to form a sticky plaque biofilm on teeth, which gives rise to severe childhood tooth decay that affects millions of children worldwide. In his award-winning study, titled “Interkingdom Assemblages in Saliva Display Group-Level Migratory Surface Mobility”, Dr. Ren discovered that bacteria and fungi naturally present in the saliva of toddlers with severe decay can form superorganisms able to move and rapidly spread on tooth surfaces.

Justin Burrell

Justin Burrell won second place in the AADOCR Hatton Competition postdoctoral category for his research. Dr. Burrell has been working with Dr. Anh Le in Penn Dental Medicine’s Department of Oral Surgery/Pharmacology and Dr. D. Kacy Cullen of Penn Medicine and Penn Bioengineering. Together, their interdisciplinary team of clinician-scientists, biologists, and neuroengineers have been developing novel therapies to expedite facial nerve regeneration and increase meaningful functional recovery.

Marshall Padilla

Marshall Padilla earned third place at the Society for Biomaterials Postdoctoral Recognition Award Competition for a project titled, “Branched lipid architecture improves lipid-nanoparticle-based mRNA delivery to the liver via enhanced endosomal escape”. Padilla was also a finalist in the AADOCR Hatton Award Competition, presenting on a separate project titled, “Lipid Nanoparticle Optimization for mRNA-based Oral Cancer Therapy”. Both projects employ lipid nanoparticles, the same delivery vehicles used in the mRNA COVID-19 vaccine technology. A postdoctoral fellow in the lab of Dr. Michael J. Mitchell of Penn’s Department of Bioengineering, Dr. Padilla’s research focuses on developing new ways to enhance the efficacy and safety of lipid nanoparticle technology and its applications in dentistry and biomedicine. He has been working in collaboration with Dr. Shuying (Sheri) Yang and Dr. Anh Le in Penn Dental Medicine.

Dennis Sourvanos

Dennis Sourvanos (GD’23, DScD’23) was the recipient of the Trainee Travel Grant award through the Osteology Foundation (Lucerne Switzerland). Dr. Sourvanos will be presenting his research related to medical dosimetry and tissue regeneration at the International Osteology Symposium in Barcelona, Spain (April 27th – 29th 2023). He also presented at the 2023 AADOCR/CADR Annual Meeting for his project titled, “Validating Head-and-Neck Human-Tissue Optical Properties for Photobiomodulation and Photodynamic Therapies.” Dr. Sourvanos has been working with Dr. Joseph Fiorellini in Penn Dental Medicine’s Department of Periodontics and Dr. Timothy Zhu in the Hospital of the University of Pennsylvania’s Department of Radiation Oncology and the Smilow Center for Translational Research (and member of the Penn Bioengineering Graduate Group).

Read the full announcement in Penn Dental Medicine News.

Michael Mitchell and Kyle Vining Win IDEA Prize from CiPD and Penn Health-Tech

Michael J. Mitchell
Kyle Vining

 Michael J. Mitchell, J. Peter and Geri Skirkanich Assistant Professor of Innovation in Bioengineering, and Kyle Vining, Assistant Professor in Materials Science and Engineering and in Penn Dental Medicine and member of the Penn Bioengineering Graduate Group, have been awarded the second-annual IDEA (Innovation in Dental Medicine and Engineering to Advance Oral Health) Prize, issued by the Center for Innovation & Precision Dentistry (CiPD) and Penn Health-Tech.

“Through their collaborative research, they are aiming to develop next-generation treatments for dental caries (tooth-decay) using lipid nanoparticles, the same delivery vehicles employed in the mRNA COVID-19 vaccine technology.

‘This project shows the type of innovative ideas and collaborations that we are kickstarting through the IDEA prize,’ says Dr. Michel Koo, co-director of the CiPD and Professor at Penn Dental Medicine. ‘This is a great example of synergistic interaction at the interface of engineering and oral health’ adds Dr. Kate Stebe, co-director of the CiPD and Professor at Penn Engineering.”

Read the full announcement in Penn Dental Medicine News.

Penn Medicine and Independence Blue Cross Eliminate Preapprovals for Imaging Tests

Brian Litt, MD

Brian Litt, Professor in Bioengineering in Penn Engineering and in Neurology in the Perelman School of Medicine, spoke to Neurology Today about the advances in technology for detecting and forecasting seizures.

The Litt Lab for Translational Neuroengineering translates neuroengineering research directly into patient care, focusing on epilepsy and a variety of research initiatives and clinical applications.

“Dr. Litt’s group is working with one of a number of startups developing ‘dry’ electrode headsets for home EEG monitoring. ‘They are still experimental, but they’re getting better, and I’m really optimistic about the possibilities there.'”

Read “How Detecting, Identifying and Forecasting Seizures Has Evolved” in Neurology Today.

Read more stories featuring Litt in the BE Blog.

Study Reveals New Insights on Brain Development Sequence Through Adolescence

by Eric Horvath

3D illustration of a human brain
Image: Courtesy of Penn Medicine News

Brain development does not occur uniformly across the brain, but follows a newly identified developmental sequence, according to a new Penn Medicine study. Brain regions that support cognitive, social, and emotional functions appear to remain malleable—or capable of changing, adapting, and remodeling—longer than other brain regions, rendering youth sensitive to socioeconomic environments through adolescence. The findings are published in Nature Neuroscience.

Researchers charted how developmental processes unfold across the human brain from the ages of 8 to 23 years old through magnetic resonance imaging (MRI). The findings indicate a new approach to understanding the order in which individual brain regions show reductions in plasticity during development.

Brain plasticity refers to the capacity for neural circuits—connections and pathways in the brain for thought, emotion, and movement—to change or reorganize in response to internal biological signals or the external environment. While it is generally understood that children have higher brain plasticity than adults, this study provides new insights into where and when reductions in plasticity occur in the brain throughout childhood and adolescence.

The findings reveal that reductions in brain plasticity occur earliest in “sensory-motor” regions, such as visual and auditory regions, and occur later in “associative” regions, such as those involved in higher-order thinking (problem solving and social learning). As a result, brain regions that support executive, social, and emotional functions appear to be particularly malleable and responsive to the environment during early adolescence, as plasticity occurs later in development.

“Studying brain development in the living human brain is challenging. A lot of neuroscientists’ understanding about brain plasticity during development actually comes from studies conducted with rodents. But rodent brains do not have many of what we refer to as the association regions of the human brain, so we know less about how these important areas develop,” says corresponding author Theodore D. Satterthwaite, the McLure Associate Professor of Psychiatry in the Perelman School of Medicine, and director of the Penn Lifespan Informatics and Neuroimaging Center (PennLINC).

Read the full story in Penn Medicine News.

N.B.: Theodore Satterthwaite in a member of the Penn Bioengineering Graduate Group.