The Lankenau Institute for Medical Research
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.”
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
LIMR Associate Professor Alexander J. Muller, PhD, has been invited to present a lecture titled, “From pregnancy to onco-inflammation with the immune modulator, IDO,” at the 2014 International Symposium on Molecular Medicine and Infectious Disease sponsored by the Drexel University College of Medicine Institute for Molecular Medicine and Infectious Disease. The symposium will take place from June 16-20, 2014 in Geary Auditorium B, at New College Building on the Drexel University College of Medicine’s Center City Campus, 245 North 15th Street, Philadelphia, Pennsylvania. Detailed information regarding the Symposium is available on the Institute website, drexelmed.edu/immid.
In 2005 Dr. Muller, in collaboration with LIMR President and CEO Dr. George Prendergast, PhD, showed how tumors can switch on a gene called IDO1 that is involved in protecting the fetus from being rejected by the mother’s immune system. The research demonstrated for the first time how an experimental drug that blocks IDO1 might be used to dramatically improve responses to treatment with standard chemotherapy by unleashing an anti-tumor immune response. Now, this novel approach to treating cancer is being tested in breast cancer patients, with the Main Line Health hospitals at the forefront of this groundbreaking clinical study. Dr. Muller will discuss ongoing studies probing into the complex immunological, cellular and molecular consequences of targeting IDO1 in the context of cancer treatment so as to better understand how to optimize patient care.
LIMR President and CEO George Prendergast, PhD was invited to speak at Mount Desert Island Biological Laboratory in Maine September 9th to discuss LIMR’s innovative model of translational research. Termed ‘acapreneurialism’ by Dr. Prendergast, LIMR’s culture marries basic and preclinical research with intellectual property development, clinical research studies and commercial avenues of discovery in order to produce meaningful medical breakthroughs. This unique research model envisioned by Dr. Prendergast has propelled LIMR into the forefront of biotechnology, developing research tools, diagnostic tests, and therapeutics that are clinically relevant while being created in a more streamlined process. Watch The Business of Science: Making Science Work for Society.
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.
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.
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.
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.
LIMR is extremely grateful to the estate of Dorothy Merritt Jones Shumen, a consummate supporter of our research programs. A donation of $232,000 was recently received from the Shumen family to fund promising research opportunities at LIMR. If you would like to make a donation or designate a gift to LIMR, please visit our Giving Opportunities page, or contact David Phillips, Executive Director of Development, at 484-476-8070.
The 12th Annual Fight from the Fairway, a charity golf tournament sponsored by Weston Solutions, has raised $11,500 this year for LIMR’s breast cancer research program. The event is run by both current and former employees of Weston, who has been raising funds for over a decade to increase awareness and knowledge about breast cancer and breast health and to help eradicate the disease through clinical research. Weston has given over $350,000 towards breast cancer research and education in memory of former employee Karen Schneider.
"Continuing its proud tradition, the Fight from the Fairway team continues to be one of our most dedicated supporters in the fight against breast cancer by Lankenau researchers,” stated George Prendergast, PhD, Professor, President and CEO of LIMR. “Thanks to the stalwart leadership of Weston Solutions and the generous donors who support this golf tournament, LIMR scientists have taken a prognostic biomarker they discovered for breast cancer and have begun to turn it into a target for antibodies that can specifically attack the breast cancer. This exciting development, made possible by the funds raised by Fight from the Fairway, shows how a group of dedicated individuals can help advance research for improved patient care and medicine."
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.
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.
NewLink Genetics Corporation (NASDAQ:NLNK), an oncology-focused biopharmaceutical company specializing in immunotherapy, announced that it has been selected for addition to the NASDAQ Biotechnology Index (NASDAQ:NBI), effective prior to the market open on Monday, May 20, 2013. NewLink, based in Ames, Iowa, has an exclusive license to LIMR technology for the development of specific IDO inhibitors to treat cancer by enhancing the ability of chemotherapy to destroy tumor cells.
The NASDAQ Biotechnology Index is designed to track the performance of a set of NASDAQ-listed securities classified as either Biotechnology or Pharmaceuticals. These companies must meet eligibility criteria that include a minimum market capitalization of $200 million and a minimum average daily trading volume of 100,000 shares. For more information about the NASDAQ Biotechnology Index, visit www.nasdaq.com.
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), 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 OxPhosTM, 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.
Eunoia Biotech, the newest member of the LIMR Biotech Incubator, is a preclinical-stage company developing nanotherapeutics and nanoparticle formulations for targeted delivery. Their patented technology can be tailored for a wide range of applications including improving pharmacokinetics (PK), enhancing drug efficacy, and delivering biologic drugs to intracellular targets.
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 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.
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.
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.
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.
On Wednesday, May 22, LMC patients, families, friends and visitors celebrated Cancer Survivor Day at Lankenau. The annual event was held in the Annenberg Center and included hors d’oeuvres, presentations by Lankenau staff, exhibit tables, and artwork created by people who have been touched by cancer. The theme of the event, Food for Body and Soul, highlighted the importance of eating healthy, staying fit, and having a positive outlook in life.
LIMR researchers like Maggie Wallon, PhD, presented their findings, as well as some of the diagnostic assays that have been invented by scientists at Lankenau. Guests appreciated the fact that their participation in LIMR’s clinical trials and programs enable new tests and treatments to be developed that will benefit them and others dealing with cancer.
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:
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.
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.
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