Category: faculty

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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.

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César de la Fuente Receives 2023 Rao Makineni Lectureship Award

by Holly Wojcik

César de la Fuente
César de la Fuente

The American Peptide Society has selected César de la Fuente, Presidential Assistant Professor in Psychiatry, Microbiology, Bioengineering and in Chemical and Biomolecular Engineering, as the recipient of the prestigious 2023 Rao Makineni Lectureship Award.

Presented at the biennial American Peptide Symposium, the Makineni Lectureship Award recognizes an individual who has made a recent contribution of unusual merit to research in the field of peptide science, and is intended to acknowledge original and singular discoveries.

Established in 2003 by an endowment by PolyPeptide Laboratories and Murray and Zelda Goodman, this lectureship honors Rao Makineni, a long-time supporter of peptide science, peptide scientists, and the American Peptide Society.

This story originally appeared in Penn Engineering Today.

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Breaking Down Barriers to Blood Donation for LGBTQ+ People

by Meredith Mann

Close-up of a person's arm and hand as they donate blood.
(Image: iStock/hxdbzxy)

For decades, LGBTQ+ patients have faced stringent requirements to donate blood—most gay and bisexual men were not allowed to donate at all. Now, however, many more of them will be able to give this selfless gift. The U.S. Food and Drug Administration, which regulates blood donation in this country, has reworked the donor-screening criteria, and in the process opened the door to donation for more Americans.

The previous restriction on accepting blood from men who have sex with men (MSM) dates back to the early days of the AIDS epidemic, when blood donations weren’t able to be screened for HIV, leading to cases of transfusion-transmitted HIV. In 1985, the FDA instituted a lifetime ban on blood donation for MSM, effectively preventing gay and bisexual men from donating. (Also included were women who have sex with MSM.)

Twenty years later, the agency rescinded the ban—but added a restriction that only MSM who had been abstinent from sex for at least one year could donate. In 2020, the FDA shortened the “deferral” period to 90 days of abstinence. While the changes were welcome news for those who had been unable to donate, they still prevented many MSM from giving blood. As he wrote in an op-ed for the Philadelphia Inquirer last year, Kevin B. Johnson, the David L. Cohen University Professor with appointments in the School of Engineering and Applied Science, the Perelman School of Medicine, and Annenberg School for Communication, was one of them. He and his husband were shocked to learn when they went to donate blood during a shortage early in the COVID-19 pandemic, that despite being married and monogamous for close to 17 years, they could not donate unless they were celibate for three months.

“It is time to move quickly to a policy under which all donors are evaluated equally and fairly, and to encourage local blood collection facilities to comply with that policy,” Johnson wrote last year.

Now, such changes are underway. As the pandemic wound down, the FDA moved forward with plans to re-evaluate its donation criteria. The first big change was removal of an indefinite ban on people who lived in or spent significant amounts of time in the United Kingdom, Ireland, and France, a measure that aimed to protect the U.S. blood supply against Creutzfeldt-Jakob disease (CJD; also known as “mad cow disease”), a terminal brain condition caused by hard-to-detect prions that occurred in those countries in the 1980s and 1990s.

Extensive and careful evaluation of epidemiological studies and statistical analysis has shown that the risk of CJD transmission is no longer a concern. The changes to eligibility for LGBTQ+ patients are related to advances in medical and social science, and have also been very thoroughly studied to ensure that the changes will maintain the safety of the blood supply without being discriminatory.

“In the decades since HIV was first recognized, there have been advances in testing methods for detection of the virus, changes in how we process blood products, public health advances, and extensive study of the evolving risk of disease transmission given these advances,” says Sarah Nassau, vice chair of pathology and laboratory medicine at Lancaster General Hospital.

They also draw on rethinking the reliability of the guidelines. For example, while the rules partially or fully prevented gay and bisexual men from donating blood, they did not erect similar barriers to other people engaging in anal sex, or people who have multiple partners.

“Specifying the sexual orientation of the person rather than a behavior in which they engaged was discriminatory and not evidence based,” points out Judd David Flesch, vice chief of inpatient operations in the Department of Medicine at Penn Presbyterian Medical Center and co-director of the Penn Medicine Program for LGBT Health.

Read the full story in Penn Medicine News.

Kevin Johnson is the David L. Cohen University of Pennsylvania Professor in the Departments of Biostatistics, Epidemiology and Informatics and Computer and Information Science. As a Penn Integrates Knowlegde (PIK) University Professor, Johnson also holds appointments in the Departments of Bioengineering and Pediatrics, as well as in the Annenberg School of Communication.

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Penn Dental Medicine Collaboration Identifies New Bacterial Species Involved in Tooth Decay

S. sputigena cells form a honeycomb-like structure that encapsulates S. mutans to greatly increase and concentrate acid production that boost caries development and severity.
Image: Courtesy of Penn Dental Medicine

Collaborating researchers from the University of Pennsylvania School of Dental Medicine and the Adams School of Dentistry and Gillings School of Global Public Health at the University of North Carolina have discovered that a bacterial species called Selenomonas sputigena can have a major role in causing tooth decay.

Scientists have long considered another bacterial species, the plaque-forming, acid-making Streptococcus mutans, as the principal cause of tooth decay—also known as dental caries. However, in the study, published in Nature Communications, the Penn Dental Medicine and UNC researchers showed that S. sputigena, previously associated only with gum disease, can work as a key partner of S. mutans, greatly enhancing its cavity-making power.

“This was an unexpected finding that gives us new insights into the development of caries, highlights potential future targets for cavity prevention, and reveals novel mechanisms of bacterial biofilm formation that may be relevant in other clinical contexts,” says study co-senior author Hyun (Michel) Koo, a professor in the Department of Orthodontics and Divisions of Pediatrics and Community Oral Health and co-director of the Center for Innovation & Precision Dentistry at Penn Dental Medicine.

The other two co-senior authors of the study were Kimon Divaris, professor at UNC’s Adams School of Dentistry, and Di Wu, associate professor at the Adams School and at the UNC Gillings School of Global Public Health.

“This was a perfect example of collaborative science that couldn’t have been done without the complementary expertise of many groups and individual investigators and trainees,” Divaris says.

Read the full story in Penn Today.

Michel Koo is a professor in the Department of Orthodontics and divisions of Community Oral Health and Pediatric Dentistry in Penn Dental Medicine and co-director of the Center for Innovation & Precision Dentistry. He is a member of the Penn Bioengineering Graduate Group.

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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.

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RNA Nanoparticle Therapy Stops the Spread of Incurable Bone Marrow Cancer

by Melissa Pappas

Myeloma cells producing monoclonal proteins of varying types, created by Scientific Animations under the Creative Commons Attributions-Share Alike International 4.0 License

Multiple myeloma is an incurable bone marrow cancer that kills over 100,000 people every year. Known for its quick and deadly spread, this disease is one of the most challenging to address. As these cancer cells move through different parts of the body, they mutate, outpacing possible treatments. People diagnosed with severe multiple myeloma that is resistant to chemotherapy typically survive for only three to six months. Innovative therapies are desperately needed to prevent the spread of this disease and provide a fighting chance for those who suffer from it.

Michael Mitchell, J. Peter and Geri Skirkanich Assistant Professor of Innovation in Bioengineering (BE), and Christian Figueroa-Espada, doctoral student in BE at the University of Pennsylvania School of Engineering and Applied Science, created an RNA nanoparticle therapy that makes it impossible for multiple myeloma to move and mutate. The treatment, described in their study published in PNAS, turns off a cancer-attracting function in blood vessels, disabling the pathways through which multiple myeloma cells travel.

By shutting down this “chemical GPS” that induces the migration of cancer cells, the team’s therapy stops the spread of multiple myeloma, helping to eliminate it altogether.

Read the full story in Penn Engineering Today.

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Engineered White Blood Cells Eliminate Cancer

by Melissa Pappas

“Macrophages killing cancer cell” photographed by Susan Arnold.

By silencing the molecular pathway that prevents macrophages from attacking our own cells, Penn Engineers have manipulated these white blood cells to eliminate solid tumors.

Cancer remains one of the leading causes of death in the U.S. at over 600,000 deaths per year. Cancers that form solid tumors such as in the breast, brain or skin are particularly hard to treat. Surgery is typically the first line of defense for patients fighting solid tumors. But surgery may not remove all cancerous cells, and leftover cells can mutate and spread throughout the body. A more targeted and wholistic treatment could replace the blunt approach of surgery with one that eliminates cancer from the inside using our own cells.

Dennis Discher, Robert D. Bent Professor in Chemical and Biomolecular Engineering, Bioengineering, and Mechanical Engineering and Applied Mechanics, and postdoctoral fellow, Larry Dooling, provide a new approach in targeted therapies for solid tumor cancers in their study, published in Nature Biomedical Engineering. Their therapy not only eliminates cancerous cells, but teaches the immune system to recognize and kill them in the future.

“Due to a solid tumor’s physical properties, it is challenging to design molecules that can enter these masses,” says Discher. “Instead of creating a new molecule to do the job, we propose using cells that ‘eat’ invaders – macrophages.”

Macrophages, a type of white blood cell, immediately engulf and destroy – phagocytize – invaders such as bacteria, viruses, and even implants to remove them from the body. A macrophage’s innate immune response teaches our bodies to remember and attack invading cells in the future. This learned immunity is essential to creating a kind of cancer vaccine.

But, a macrophage can’t attack what it can’t see.

“Macrophages recognize cancer cells as part of the body, not invaders,” says Dooling. “To allow these white blood cells to see and attack cancer cells, we had to investigate the molecular pathway that controls cell-to-cell communication. Turning off this pathway – a checkpoint interaction between a protein called SIRPa on the macrophage and the CD47 protein found on all ‘self’ cells – was the key to creating this therapy.”

Read the full story in Penn Engineering Today.

Multiple members in the biophysical engineering lab lead by Dennis Discher, including co-lead author and postdoctoral fellow and Penn Bioengineering alumnus Jason Andrechak and Bioengineering Ph.D. student Brandon Hayes, contributed to this study. The research was funded by grants from the National Heart, Lung, and Blood Institute and the National Cancer Institute, including the Physical Sciences Oncology Network, of the US National Institutes of Health.

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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.

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View the 2023 Department of Bioengineering Juneteenth Address by Dr. Kevin B. Johnson

Thank you to everyone who attended the 2023 Department of Bioengineering Juneteenth Address. For those who were unable to attend or who may wish to share the opportunity to view the lecture, a recording of Dr. Kevin Johnson’s talk, “A White Neighbor, a Black Surgeon, and a Mormon Computer Scientist Walk into a Bar…” is available below.

Speaker:
Kevin B. Johnson, MD, MS, FAAP, FAMIA, FACMI
David L. Cohen University Professor
Computer and Information Science
Biostatistics, Epidemiology and Informatics
Bioengineering
Annenberg School for Communication
Pediatrics
VP for Applied Informatics (UPHS), University of Pennsylvania

Abstract:
As we recognize Juneteenth, a holiday that brings awareness to what journalist Corey Mitchell calls “…a complex understanding of the nation’s past,” we also need to understand how many of our neighbors, staff, and faculty — even those born in the last 100 years — continue to navigate through the environment that made Juneteenth remarkable. In this talk, Dr. Johnson  shares a bit of his personal story and how this story informs his national service and passion for teaching.

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On a Different Wavelength, Nader Engheta Leads a Community in Light

Nader Engheta was puzzled when he got a call from the psychology department about a fish.
In the early 1990s, Engheta, a newly minted associate professor of electrical engineering in Penn’s School of Engineering and Applied Science, was a respected expert in radio wave technologies. But in recent years, his work had been expanding into subjects at once more eccentric and fundamental.

Nader Engheta was puzzled when he got a call from the psychology department about a fish.

In the early 1990s, Engheta, a newly minted associate professor of electrical engineering in Penn’s School of Engineering and Applied Science, was a respected expert in radio wave technologies. But in recent years, his work had been expanding into subjects at once more eccentric and fundamental.

Engheta’s interest in electromagnetic waves was not limited to radio frequencies, as a spate of fresh publications could attest. Some studies investigated a range of wave interactions with a class of matter known as a “chiral media,” materials with molecular configurations that exhibit qualities of left or right “handedness.” Others established practical electromagnetic applications for a bewildering branch of mathematics called “fractional calculus,” an area with the same Newtonian roots as calculus proper but a premise as eyebrow-raising as the suggestion a family might literally include two-and-a-half children.

Electromagnetic waves are organized on a spectrum of wavelengths. On the shorter end of the spectrum are high-energy waves, such as X-rays. In the middle, there is the limited range we see as visible light. And on the longer end are the lower-energy regimes of radio and heat.

Researchers tend to focus on one kind of wave or one section of the spectrum, exploring quirks and functions unique to each. But all waves, electromagnetic or not, share the same characteristics: They consist of a repeating pattern with a certain height (amplitude), rate of vibration (frequency), and distance between peaks (wavelength). These qualities can define a laser beam, a broadcasting voice, a wind-swept lake, or a violin string.

Engheta has never been the kind of scholar to limit the scope of his curiosity to a single field of research. He is interested in waves, and his fascination lies equally in the physics that determine wave behavior and the experimental technologies that push the boundaries of those laws.

So, when Edward Pugh, a mathematical psychologist studying the physiology of visual perception, explained that green sunfish might possess an evolutionary advantage for seeing underwater, Engheta listened.

Soon, the two Penn professors were pouring over microscope images of green sunfish retinas.

Read Devorah Fischler’s full story about Nader Engheta and watch an accompanying video at Penn Today.

Nader Engheta is H. Nedwill Ramsey Professor of Electrical and Systems Engineering at Penn Engineering, with secondary appointments in the departments of Bioengineering, Materials Science and Engineering, and Physics and Astronomy in the School of Arts & Sciences.