Penn Medicine AIDS Researcher: $16.3 Million from NIH to Accelerate HIV Vaccine Development Research
Building on earlier work in designing chimeric human-simian immunodeficiency viruses (SHIVs) that serve as a model of HIV infection in humans, George M. Shaw, a professor of hematology/oncology and microbiology in the Perelman School of Medicine at the University of Pennsylvania, has received $16.3 million over five years from the National Institute of Allergy and Infectious Diseases (NIAID) to develop a long-sought-after HIV vaccine. The research is premised on the human body’s capacity, in rare individuals, to produce broadly neutralizing antibodies against HIV in the course of natural infection, and the hypothesis that SHIV infection of monkeys could do the same.
Despite decades of research, there are still no HIV vaccines for humans that can induce the body to make the broadly neutralizing antibodies viewed as capable of conferring protective immunity against the virus. Antibodies defend cells by blocking the invasion of foreign pathogens. Similar to other vaccines, an HIV vaccine would introduce non-infectious components or a weakened form of the microbe to a person’s immune cells, readying them for a possible future attack against a microbe they have already been exposed to.
A major reason for the elusiveness of an HIV vaccine—despite a number of promising candidates—is the virus’s ability to rapidly mutate or otherwise conceal its outer coat proteins, known as the envelope. The envelope fuses with the host cell, allowing viral genes to enter the host cell and replicate, eventually leading to cell death. Another problem is that the envelope is coated with sugars derived from the body, which a person’s immune system does not recognize as foreign and hence won’t readily attack. But envelopes can elicit, albeit in the case of HIV only after several years of infection and only in a subset of people, the antibodies that could ultimately lead to their very demise. It is this capacity that serves as a foundation in the search for an HIV vaccine.
In an effort to overcome these envelope-based obstacles, the NIAID grant will allow the researchers, for the first time, to model the development of broadly neutralizing antibodies in SHIV-infected rhesus macaque monkeys. The investigators expect such antibodies to occur more commonly in the monkeys than they do in human HIV infection and at an accelerated pace. The basis for this speculation is preliminary data by the Penn team that showed that HIV envelopes that elicited broadly neutralizing antibodies in humans did the same in monkeys. If these findings are generalized in the newly funded work, it should be possible using molecular cloning approaches to isolate unique combinations of rhesus and human antibody precursors and HIV envelopes that bind them with high affinity. And this could serve as a basis of a new HIV vaccine development strategy.
In the proposed new work, Dr. Shaw and his team will seek to induce broadly neutralizing antibodies in rhesus monkeys via laboratory-created simian-human immunodeficiency viruses. SHIVs, which contain HIV envelopes from humans that elicited broadly neutralizing antibodies or were found to bind to precursors of these antibodies, will be used to infect monkeys. Then, the maturation or evolution of these antibody precursors will be characterized genetically along with sequences of the HIV envelope as they co-evolve throughout infection. Such a strategy, the investigators believe, will allow them to decipher the critical molecular events responsible for eliciting broadly neutralizing antibodies. This, in turn, can serve as a “molecular guide” for designing vaccine immunogens that reproduce the antibody-eliciting behavior of SHIV or HIV infections.
The new funding comes in the wake of a study from the Shaw lab published in the Proceedings of the National Academy of Sciences last year that may become a signal event in the HIV/AIDS vaccine effort. It addressed a major problem with SHIVs: the only HIV envelopes that would allow SHIVs to infect rhesus monkeys were artificially adapted to bind to the rhesus CD4 molecule, the primary receptor for the virus. Unfortunately, as a side-effect, the SHIV envelopes lost their natural defenses to antibodies, effectively erasing their potential value for HIV vaccine research. To surmount this problem, the Shaw team found that changing a single amino acid in what is called the “CD4 binding pocket”—out of about 850 that comprise the viral envelope—led to a much greater ability of SHIVs to infect rhesus monkeys, while at the same time retaining the basic features of the normal HIV envelope and its interaction with the human immune system.
Building on these findings, the Shaw team will test a large panel of novel SHIVs that each carry an envelope known to bind broadly neutralizing antibodies. SHIVs will be down-selected to a manageable number based on their ability to elicit strong antibody responses, which in turn will be assessed for breadth of reactivity against hundreds of different HIV strains that circulate globally. Those SHIVs that elicit the most potent and broadly reactive antibodies will then be subjected to intensive analysis in larger numbers of animals where patterns of antibody–envelope coevolution will be assessed.
Finally, recombinant-DNA-generated protein immunogens that mimic the structure and antigenicity of envelopes from immunogenic SHIVs will be tested for their ability to elicit broadly neutralizing antibodies in rhesus macaques. If successful in the monkeys, analogous immunogens could be advanced to human trials.
Other members of the team are Hui Li and Beatrice Hahn from Penn; Barton Haynes and Garnett Kelsoe from Duke University; Steve Harrison from Harvard University; and Bette Korber from the Los Alamos National Laboratories.
$10 Million from Ken Moelis and Julie Taffet Moelis for Wharton MBA
The Wharton School of the University of Pennsylvania is pleased to announce that Ken Moelis, W’80, WG’81, and Julie Taffet Moelis, W’81, have made a $10 million gift to establish the Ken Moelis and Julie Taffet Moelis Advance Access Program, a deferred admission opportunity that will provide a pathway to a Wharton MBA for highly-qualified Penn undergraduates whose academic and career interests expand traditional notions of business education.
The program adds to the School’s existing Submatriculation Program with a deferred-enrollment plan for the most competitive candidates, enabling them to apply and gain guaranteed admission as undergraduates, work for several years, and return to Wharton for their MBA. It opens access to all Penn undergraduate students who aspire to set the stage early for their advanced education and highly successful careers. Ultimately, the program will expand to allow applications from the best undergraduate institutions across the United States and around the world.
“We strive to adapt and continue to draw the best and the brightest to Wharton, preparing them to become leaders and trendsetters in today’s rapidly changing environment,” said Wharton Dean Geoffrey Garrett. “Ken and Julie are helping us do just that—reimagining the Wharton Submatriculation Program so that it provides a new route to the Wharton MBA for outstanding undergraduates from all academic backgrounds, one that nurtures exploration, strategic risk-taking, and discovery, and enables our students to use their business education to change the world.”
In the Moelis Advance Access Program, undergraduates may apply to the MBA Program during their senior year and, for those admitted, enter the workforce for two to four years before returning to Wharton for graduate school. During this time, students will be empowered to pursue job opportunities in a range of fields, including those that capture their greatest interest and extend beyond the conventional definitions of business. They will also engage in the program and with their future classmates through professional development, mentoring opportunities, and social events.
“In my personal experience as a submatric student, and now as CEO of a firm that recruits top MBAs from across the country, it is clear that ambitious students with unique aspirations do not always benefit from the one-size-fits-all track for MBAs,” said Mr. Moelis. “Julie and I are excited to unlock the potential of these students—to help them consider an expanded view of the fields that need their leadership and gain valuable, practical experience after completing their undergraduate degree and before starting their MBA.”
Mr. and Mrs. Moelis’ generosity will also provide financial assistance for selected students in this program. Students in the program will be considered for a $10,000 fellowship each year during the two-year full-time MBA program in addition to other financial aid awards.
The Moelis Advance Access Program helps Penn retain exceptional students from across the University—the College of Arts and Sciences, the School of Engineering and Applied Science, the School of Nursing, the Wharton School, and coordinated dual-degree programs—to continue their graduate degree at Penn through the MBA program. In the future, adding to the Penn students in the program, it will grow to provide an amazing and elite opportunity for outstanding students from other undergraduate institutions as well.
“Increasing access to a Penn education is a pillar of the Penn Compact 2020, and I am so grateful to Ken and Julie for creating innovative ways to expand educational opportunity through their amazing commitment,” said Penn President Amy Gutmann. “Ken and Julie are encouraging students to think early about their graduate degree, venture into diverse fields after graduation, and bring these robust, interdisciplinary experiences to their Wharton MBA journey.”
The results lie in the future generations of Moelis Fellows, the proud graduates who promise to shape a range of important and emerging industries—from analytics, to health care and beyond. Students who participate in the new deferred-enrollment plan as well as those who complete their BS/MBA in five years as part of the existing Submatriculation Program will share the title, support and distinction of being Moelis Fellows.
Mr. Moelis is founder, chairman and CEO of Moelis & Company, a global independent investment bank. He is a member of Wharton’s Board of Overseers—a board he has served on for over a decade—and a Trustee of the University of Pennsylvania. A graduate of Wharton’s existing Submatriculation Program, Mr. Moelis earned his undergraduate degree in 1980 and his MBA in 1981. Mrs. Moelis is also a Wharton graduate, earning her undergraduate degree in 1981. She and Mr. Moelis are proud Wharton parents.
For more information about the Ken Moelis and Julie Taffet Moelis Advance Access Program click here.
An information session will be held for Penn undergrads interested in learning about this program; April 19, 5:30-7:30 p.m., rm. F85, JMHH.
$3 Million Gift to Establish the Ralph L. Brinster President’s Distinguished Professorship in Honor
Through the generosity of Henrietta Alexander, Penn Vet will establish the Ralph L. Brinster President’s Distinguished Professorship in honor of Ralph Brinster, renowned faculty member, scientist and National Medal of Science laureate. The Professorship will allow Penn Vet to recruit a faculty member who will contribute to the preeminence of the School and University.
The $3 million gift exemplifies Henrietta Alexander’s ongoing commitment to animal and human health, and further extends her family’s rich history at the University of Pennsylvania, dating back to the late 19th century, when Ms. Alexander’s great-grandfather, John B. Deaver, graduated from Penn’s School of Medicine.
“I wanted to make a gift that would have lasting impact, and Penn Vet was an obvious choice given my long-standing relationship with Dr. Brinster through the Kleberg Foundation, and my family’s long legacy at Penn Medicine,” said Ms. Alexander. “It is an expression of both my ongoing confidence in Penn Vet and my admiration for Dr. Brinster. His transformational work has set global standards in research and innovation in animal and human health.”
The Professorship is named for Ralph Brinster, the Richard King Mellon Professor of Reproductive Physiology at Penn Vet and a trailblazer in the development of techniques for manipulating the cellular and genetic composi tion of early mouse embryos. These techniques have made the mouse the major genetic model for understanding the basis of animal biology and disease. He began his work by showing how mouse embryos could be cultured in a Petri dish and then showing how non-embryo cells could be added to such cultured embryos to make animals of mixed cell origin, or chimeras, which first demonstrated a method to modify the germline. He is often referred to as the founder of the field of mammalian transgenesis, with its applications to human disease models and biotechnology. In recent years, he has developed new models of germline manipulation using sperm progenitor cell transplants. His findings have served as the foundation for genetic engineering, embryonic stem cell research, in vitro fertilization, knockout technology and cloning. His range of contributions is unmatched in the field.
For his groundbreaking work, Dr. Brinster was awarded the National Medal of Science in 2010, making him the first and only veterinarian to receive the prestigious award, and one of only eight scientists at the University of Pennsylvania to receive this distinction in the last 50 years.
“We are incredibly grateful to Henrietta Alexander for her commitment to innovative research in the veterinary field and for this generous gift, which honors Ralph’s pioneering work while allowing us to recruit a faculty member who will continue this legacy of excellence,” said Joan C. Hendricks, the Gilbert S. Kahn Dean of Veterinary Medicine. “Ralph is extraordinarily humble, but was persuaded to accept this gift in his name because it will continue to support scholarship of the caliber and in the field that he established. Since Ralph also established the VMD-PhD program that gave me my start, I am personally gratified to see a permanent professorship in his name established at the school we both love.”
Ms. Alexander, who grew up on a farm near Penn Vet’s New Bolton Center and joined the Penn Vet Board of Overseers in 1986, learned of Dr. Brinster’s work while serving as director of the Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation. The Foundation has supported Dr. Brinster’s research program for nearly 25 years, stemming from the family’s interest in breeding quality livestock. Ms. Alexander’s grandfather, Bob Kleberg, created the Santa Gertrudis breed of cattle, and bred numerous champion quarter horses and thoroughbred racehorses as well as bird dogs. In addition, he was a pioneer for wildlife conservation and provided the impetus and funds for agricultural and scientific research in various fields worldwide.
“Henrietta has been a valued friend and a strong advocate for our research and for science for many years and shows extraordinary insight into scientific goals and their fundamental importance to animal health and human advancement,” said Dr. Brinster. “I am enormously honored and extremely grateful to have our research recognized in this distinctive manner, particularly by such a close and knowledgeable friend. I received my medical and research training at Penn Vet, which provided a strong and unique foundation for our contributions. I am grateful for the support and interactions that have come from many students, colleagues, and collaborators within the School, University and scientific community that facilitated our research. It is their talent and hard work that made our accomplishments possible.”
Perelman School of Medicine McCabe Fund Awards for FY 2018; Call for Applications: May 15
The McCabe Fund Advisory Committee is calling for applications from junior faculty in the Perelman School of Medicine (PSOM) and the School of Veterinary Medicine for the annual Thomas B. and Jeannette E. Laws McCabe Fund Fellow and Pilot Awards. The McCabe awards were established in 1969 by a generous gift from Thomas B. and Jeannette E. Laws McCabe to the Perelman School of Medicine. The purpose of this gift is to support junior faculty who initiate fresh and innovative biomedical, clinical, and surgical research projects. Eligible faculty are those who have received either limited or no external research funding while in their first through third years on the faculty at the PSOM or the School of Veterinary Medicine at Penn. Junior faculty in these schools should contact their department chair for information and application forms. The guidelines and instructions to determine eligibility are also available on the PSOM website.
The deadline for submission is Monday, May 15. The McCabe Fund Advisory Committee will select the winners at its annual meeting in June.
McCabe Fund Awards for 2017
Last year there were three winners of Fellow Awards of $40,000 each:
Rumela Chakrabarti, biomedical sciences, School of Veterinary Medicine;
Sandra Maday, neuroscience, PSOM
Panteleimon Rompolas, dermatology, PSOM
There were 20 Pilot Award winners, all from PSOM, who received $20,428 each:
Zarina S. Ali, neurosurgery
Alexander F. Arriaga, anesthesiology & critical care
Josh R. Baxter, orthopaedic surgery
Abigail T. Berman, radiation oncology
Sandhitsu R. Das, neurology
Helge D. Hartung, pediatrics
Michael W. Hast, orthopaedic surgery
Daniel S. Herman, pathology & laboratory medicine
Victoria E. Johnson, neurosurgery
Vivek Narayan, medicine
Kavindra Nath, radiology
Desmond J. Oathes, psychiatry
Mark O’Hara, medicine
Ali Kemal Ozturk, neurosurgery
Jeffrey D. Roizen, pediatrics
Kira L. Ryskina, medicine
Haochang Shou, biostatistics & epidemiology
Raymond Soccio, medicine
Samuel Swisher-McClure, radiation oncology
Eric Williamson, neurology