LIMR Link News

Feature Article

Nobel Prize-Winning Research has Roots in LIMR

Discoveries made in the 1950s by researchers at Lankenau Institute for Medical Research, then known as Lankenau Hospital Research Institute (LHRI), were the basis for this year’s Nobel Prize in Medicine received by British scientist John Gurdon. Gurdon’s work shows that normal cells of the body can be reprogrammed to create disease-fighting stem cells.

Gurdon used frog cells to demonstrate how stem cells can be created from any adult cell. In theory, Gurdon’s discovery means that a doctor might be able to utilize a patient’s own cells to create the stem cells needed to treat their disease. The methods Gurdon used were established and proven on tadpole cells by Drs. Robert Briggs and Thomas King at LHRI.

“Textbooks used to train biologists today still reference the founding LHRI paper in the stem cell field, providing a beautiful illustration of how medical advances emerge from fundamental basic research of the type conducted by LIMR scientists,” notes George Prendergast, PhD, LIMR Professor, President, and CEO. “In medicine, hope springs from research, but only where the research mission has the dedicated support of visionary organizations like Lankenau Medical Center and Main Line Health that support the foundations necessary for medical advances to blossom.”

Esteemed Chinese Cardiologist Dayi Hu Visits LIMR and LMC

Renowned cardiologist Dayi Hu, MD, FACC, FESC, of China, visited the Lankenau Institute for Medical Research and Lankenau Medical Center to meet with cardiologists, surgeons, and researchers throughout Main Line Health and to present a cardiology grand rounds lecture.

Dr. Hu is Chief of the Heart Center at Peking University People’s Hospital and Dean of the Clinical Research Institute at Shanghai’s Fudan University. A pioneer of radio-frequency ablation technology in the treatment of tachyarrhythmia, . . . Read More

Faculty Spotlight

Dr. Sawicki was Invited Speaker at International Conference on Ovarian Cancer Research

Professor and LIMR Deputy Director Janet Sawicki, PhD was invited to present a lecture at the 6th Annual International Conference on Ovarian Cancer Research held in Quebec, Canada on May 27-29. The title of her seminar was "Ovarian Cancer Nanotherapies.” Dr. Sawicki discussed preclinical studies she has conducted in 3 different ovarian cancer models to evaluate various nanotherapeutics.

Nanotherapy is the use of very small carrier molecules to deliver attached therapeutics to the specific area of the body where the cancer is located, and then bind only to those cancer cells. Advanced ovarian cancer is uniquely suited to nanoparticle-based therapies because the particles can easily be delivered directly to the peritoneal space where the primary tumor and a majority of the metastatic tumors are located.

Dr. Sawicki has delivered both DNA and siRNA, or small interfering RNA, to ovarian cancer cells via nanoparticles. The experiments with DNA delivery showed inhibition of tumor growth and an increase in lifespan of 33%. Similarly, treatment with nanoparticles bearing siRNA that silences a tight junction protein resulted in tumor shrinkage and a reduction in ascites formation.

Promising results of siRNA knockdown of an RNA-binding protein known as Human antigen R (HuR) were also presented by Dr.Sawicki. This protein regulates mRNA stability, and thus the expression, of many genes known to play a role in tumorigenesis. Apart from its potential as a therapeutic target, results of a retrospective clinical study suggest that the cellular location of HuR can be used as a predictive marker to identify those ovarian cancer patients that will respond well to gemcitabine treatment.

Li Zhang, MD

Cardiologist and LIMR Associate Professor Li Zhang, MD has been elected as a Vice President of the Chinese American Heart Association (www.CnAHA.org), a fast growing and the largest non-profit organization comprised of Chinese origin cardiologists, cardiothoracic surgeons, and cardiovascular research scientists in North America.

Last November, Dr. Zhang was invited to present her research at the American Heart Association’s President’s Reception. In January, in her role as Director of Cardiovascular Outcomes Research, Main Line Health Heart Center, Lankenau Medical Center, Dr. Zhang gave a keynote address at the Philadelphia chapter of the American Heart Association’s Go Red for Women symposium in Center City.

The Journal of Cardiovascular Disease Research has selected Dr. Zhang to be section editor for Education/CME. Currently she serves as the Director of www.cv-research-symposium.org. This online education program is co-organized by CnAHA and the Academy of Cardiovascular Research Excellence (www.theacre.org). Physicians are invited to participate in this online continued medical education (CME) program accredited by the CME Office of Lankenau Medical Center, Main Line Health.

Dr. Prendergast Writes About Tumors and Tryptophan in the Journal Nature

George Prendergast, PhD, President and CEO of LIMR, has written an article in the highly regarded journal Nature entitled ‘Why Tumours Eat Tryptophan.’ As a leading expert on immune escape, Dr. Prendergast discusses the current literature regarding tryptophan consumption and how this facilitates the progression of cancer.

Indoleamine 2,3-dioxygenase (IDO), an enzyme that has been found in tumors, degrades tryptophan into byproducts. These catabolites then bind cellular receptors that suppress T-cell proliferation. This process of immune escape can ultimately lead to aggressive tumor growth. A new study investigated the role of TDO, or tryptophan 2,3-dioxygenase, in tumor cell growth and survival. Previously, it was thought that TDO was confined to the liver, where it breaks down tryptophan in preparation for disposal by the body. The recent study has shown that TDO, like IDO, is upregulated by cancer cells and can also decrease the immune response by way of the tryptophan catabolism pathway.

This important research sheds new light on how tumors evade the body’s immune system, providing more avenues of discovery into the eradication of cancer. Read Dr. Prendergast’s Nature article, vol. 478, p. 192-194, doi:10.1038/478192a.

Clinical Research News

Dr. DeNittis Named New CCOP Principal Investigator

Albert DeNittis, MD, chief of Radiation Oncology, LMC, and LIMR Clinical Associate Professor, has accepted the position of principal investigator for the Community Clinical Oncology Program (CCOP), a National Cancer Institute sponsored Cancer Clinical Trials Program. Dr. DeNittis succeeds Paul Gilman, MD, co-medical director of the Cancer Center, LMC, and system chief of Hematology/Medical Oncology, who has stepped down after 15 years in the position. CCOP provides patients access to new cutting-edge treatments and symptoms management for cancer. The program is available to Main Line Health patients at Lankenau, Bryn Mawr, and Paoli Hospitals. To learn more about this program, contact Diana Blade, CCOP Administrator, at 484.476.2649 or BladeD@mlhs.org.

Funding Highlights

George Prendergast, PhD Awarded 2 NIH Grants to Study IDO Inhibitors as Cancer Treatments

George Prendergast, PhD has been awarded two NIH grants to support his laboratory’s investigation of IDO cancer therapeutics and IDO’s role in immune escape. IDO inhibitors are among the ‘top 10’ experimental agents that could cure cancer, according to a National Cancer Institute workshop.

The first 5-year grant of almost $1.3 million dollars will continue research into the role of IDO in circumventing the immune response. Dr. Prendergast’s group hopes to develop clinically applicable IDO inhibitors which, when combined with standard-of-care chemotherapy and radiotherapy, will stimulate the immune system to attack tumors. This innovative approach to cancer therapy, called immunochemotherapy, may lower overall treatment costs.

The second award of over $400,000 for a period of 2 years will allow for ongoing research of IDO2 inhibitors specifically for the treatment of pancreatic adenocarcinoma. This research complements the Phase I clinical trial of D-1MT, an IDO inhibitor that was shown by LIMR scientists to synergistically enhance the body’s anti-tumor response when given with chemotherapy.

Susan G. Komen For The Cure Grants Alexander Muller, PhD Funds for Metastasis Research

The Susan G. Komen for the Cure® Foundation, the global leader of the breast cancer movement, has awarded a $600,000 grant to Alexander Muller, PhD, to support metastatic breast cancer research. Previously, Dr. Muller and his group demonstrated that the IDO1 enzyme plays an important role in immune escape in tumors. The new three year grant will be applied to investigating whether IDO1 plays a similar role in secondary tumors formed by metastatic cancer. If so, blocking IDO1 in breast cancer patients may potentially slow or even halt metastatic progression, thus making standard treatment more effective.

Business Development

LCGC Collaborates with Major Pharma to Provide Large Chemical Collection
for Drug Discovery

LIMR Chemical Genomics Center, Inc. (LCGC) announced today that it has entered into a partnership that will significantly enhance translational research and new leads discovery in academia by high throughput screening (HTS). A major pharma has provided a large, structurally representative snapshot (100,000 compounds) of their proprietary chemical collection to LCGC for approved distribution to university principal investigators. This will enable more effective probing and validation of the medicinal utility of innovative cell-signaling proteins and disease pathways.

The agreement with LCGC facilitates an entirely new approach, termed Double-Blinded Drug Discovery® (DBD2), to identify and accelerate the discovery and commercialization of new drugs in fields with urgent patient need. Innovative robotic technology has been deployed that can store and rapidly retrieve up to 10 million individual chemicals. LCGC has also put into practice a more efficient HTS paradigm that enables principal investigators in academia to screen those chemicals 500% faster. These and other technologies, coupled with the new pharma collection, enable principal investigators at universities to more successfully discover new drug leads with the many assays resulting from their innovative biomedical investigations, without diluting their basic research mission. LCGC expedites information flow between the parties to further the development of new structure-activity relationships that might not occur otherwise. This new approach allows pharmaceutical companies to de-risk highly innovative targets much less expensively than by prematurely committing internal resources that could dilute drug-pipeline progression.

LCGC also provides unique opportunities for out-licensing and R&D funding to principal investigators desiring to pursue drug discovery and development with pharmas. The DBD2 consortium model has been endorsed by 13 academic organizations in the United States and internationally.

LIMR Development, Inc. (LDI) Sells First Research Product, CellCountEZ^®

LIMR Development, Inc. (LDI), a wholly-owned subsidiary of Lankenau Institute for Medical Research, handles all of LIMR’s business development initiatives. The first direct sale product released by LDI this year is CellCountEZ^®, a cell toxicity, proliferation, and survival (TPS) assay kit.

CellCountEZ^® is a tissue culture media-based assay that can measure metabolically active live cells and quantify cell death caused by radiation, chemotherapeutics, or toxins. All current approaches on the market, some in use for several decades, have a variety of disadvantages, including non-linearity, high background, and cumbersome, costly, and time-consuming protocols. There is great interest in improved methods of cell quantitation, which is important for applications in cell biology, toxicology, drug screening, and many other biosciences.

CellCountEZ^® offers many advantages that make it superior to common existing methods for quantifying cell proliferation, toxicity, and survival. CellCountEZ^® is better than other available assays because its reagents are readily soluble, membrane permeable, and converted by live cells intracellularly before transport into the extracellular culture media. There is no need to lyse cells, saving time while preserving the ability to perform other cellular tests in the same culture system. 2 simple steps make CellCountEZ^® easier and faster to use than other products on the market.

LDI also sells other research products, including immuno-modulating antibodies and OxPhos^TM, a kit that measures the antioxidant capacity of cells in tissue culture or whole blood by quantifying total glutathione recycling and function.

These and other products are available on LDI’s website, www.limrdevelopment.com, or by calling 484-476-3474.

LIMR Biotech Incubator

HaRo Pharmaceutical is the Latest Company to Join LIMR's Incubator

HaRo Pharmaceutical is an early seed-stage startup focusing on drug discovery in the area of cancer treatment. They are currently developing novel, integrated and proprietary small hybrid molecules that will modulate cell differentiation and proliferation in neural crest-derived tumors, leukemia, and other poorly differentiated cancers. HaRo's research has shown that their compounds may be specific to cancer cells, leading to better drug tolerance and fewer side effects while sparing healthy cells.

CD Diagnostics Receives Funding from Ben Franklin Technology Partners

CD Diagnostics was recently selected to receive funding from Ben Franklin Technologies, an investment group that provides critical capital, business development, and management consulting to seed and early-stage companies in southeastern Pennsylvania. According to CD Diagnostics CEO Richard Birkmeyer, “State sponsored funds have significant benefits to a start-up company. The actual dollars enable a company to move a concept through research and development, supporting both personnel and supply costs. An even greater benefit is that the funding acts as a ‘stamp of approval’ on a company when it comes from a group as widely respected as Ben Franklin.” CD Diagnostics was founded by LIMR faculty member and Lankenau orthopedic surgeon Carl Deirmengian, MD, to develop rapid, accurate tests that better diagnose the causes of joint pain.

New Addition: TegoPharm

Tegopharm Corporation is an early stage drug discovery company that focuses on developing therapeutic antibodies with dramatically improved therapeutic indices. The company's proprietary platform is based on the creation of highly-specific antibodies to diseased tissue or pathological processes. Tegopharm's patentable technology has the potential to dramatically reduce treatment limiting side effects, improving patient compliance and enabling more intensive therapy.

Noteworthy News

Mindy George-Weinstein, PhD Collaborates with Artists in 'Body Aesthetic' Show

Cell and developmental biologist Mindy George-Weinstein, PhD has long been a fan of fine art. But she has only recently lent her expertise in cell biology to friend and artist William Middleton. “Dr. George-Weinstein has been helping us to understand the mechanisms and processing pathways of the nervous system’s sensory information,” he explained. Mr. Middleton, along with glass artist James Harmon, create “electric sculptures”, artistic pieces of light wire and glass which represent different structures that perceive and respond to sensory stimuli.

Dr. George-Weinstein provided the artists with microscopy images of cells that detect light, sound, and chemicals, such as those that elicit taste sensations. She explained how these stimuli are transformed into neurochemical signals that are processed by the brain and assembled into detailed perceptions of the world around us. “The cells that detect light, sound waves and flavor-evoking chemicals are remarkably sensitive and inherently beautiful. Bill and Jim’s creations are wonderfully imaginative and educational.”

Their collaborative work is currently on exhibition at Twenty-Two Gallery, 236 S. 22nd Street, Philadelphia, PA. The show’s title, ‘Body Aesthetic’, signifies the beauty of the human body on many levels, externally as well as at the cellular level. The sculptures illustrate how the integration of art and science can enhance the beauty and understanding of both disciplines. The exhibition is ongoing until May 6th. Gallery hours are Wednesday to Sunday, 12-6pm, or by appointment.

Cell Sorter is a Crucial Resource in Targeting Disease Treatments

The Fluorescence Activated Cell Sorter, or FACS, is a core piece of instrumentation that allows scientists to distinguish and quantitate cells that are different from each other based on cellular surface markers. By separating complex populations of cells, the FACS allows the analysis of precise subpopulations of cells by molecular, biochemical, and cell function assays. In this manner, the cells can be further screened as potential targets for the treatment of cancer, autoimmune diseases, and tissue injury.

Dr. Laura Mandik-Nayak’s lab is studying the role that IDO and IDO-2 might play in the B cell-mediated immune response in arthritis. The FACS is crucial in sorting different lymphocyte subpopulations which are then assessed for differential gene expression by real-time PCR. The FACS data can be used to characterize the precise way in which the specific protein markers on healthy cells differ from those on diseased cells.

Funds to purchase and support the FACS were generously given by The Cotswold Foundation, the Charter Foundation, Main Line Health, and the Lankenau Women’s Board.

Events

LIMR Clinical Research Center to Host Celiac Awareness Program

In honor of Celiac Awareness Month, a panel of medical experts will discuss the latest news in celiac diagnosis and treatment and the gluten-free lifestyle on May 8 at Lankenau Medical Center, Annenberg Auditorium, and fed via live video conference to Bryn Mawr Hospital’s Board Room and Paoli Hospital’s Potter Room.

The program includes:

• Noon - Welcome by Robert Benz, MD, Keith Laskin, MD, and LMC President Phil Robinson
• 12:15pm – Peter H. R. Green, MD: "Update on Epidemiology, Diagnosis, and New Potential Therapies for Gluten-Related Disorders"
• 1:15pm – Steven Plogsted, PharmaD: "Gluten in Medications: Fact or Fantasy?"
• 2:15pm – Anne Lee: "The Gluten-Free Diet, What’s Next?"
• 3:30 – Panel Discussion

Screening for celiac disease will be available at Lankenau for those that qualify, and exhibitors will also be at LMC. MLH designates this educational activity for a maximum of three AMA PRA Category 1 credits. Visit www.mainlinehealth.org/paoliceliac to register. Employees, visitors and the general public are all invited to attend.

LIMR 2013 Spring Art Exhibition "Art Meets Science: Abstraction and Microscopy"

The LIMR Art Gallery is currently hosting works of art by local abstract artists Christine Stoughton, Deann Mills and Deborah Leavy. The exhibit is ongoing until June 7. Please call 484-476-8400 to schedule an appointment. Proceeds will benefit LIMR research.

Call for Applications

Undergraduate Summer 2013 Research Programs in Basic Science, Clinical, and Public Health Research

This past summer, seventeen top undergraduates spent time at LIMR conducting biomedical and public health research. The eight week summer intern program provides college students that have an interest in science and medicine the opportunity to be part of cutting-edge research aiming to improve the prevention, detection, and treatment of diseases such as cancer and cardiovascular disease. See Undergraduate Internships for more information on LIMR’s summer research programs. The deadline for submitting an application for the Summer of 2013 is February 8^th.