Author Interviews, Genetic Research, PLoS, University of Pittsburgh / 31.08.2016
Genotyping and 3D Imaging Help Identify Genes That Influence Facial Appearance
MedicalResearch.com Interview with:
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Dr. Seth Weinberg[/caption]
Seth M. Weinberg, PhD
Assistant Professor, Department of Oral Biology
Assistant Professor, Department of Anthropology
Director, CCDG Imaging and Morphometrics Lab
MedicalResearch.com: What is the background for this study?
Response: Scientists have long recognized that aspects of facial appearance have a genetic basis. This is most obvious when we look at the faces of people in the same family. It is also well known that mutations in certain genes can result in syndromes where the face is affected. However, very little is known about how specific genes influence the size and shape of normal human facial features. To date, only a handful of studies have looked at this question, and while these studies have reported several interesting results, only a small number of genes have so far been linked to normal variation in facial features. The primary goal of our study was to test for evidence of association between detailed facial measures derived from 3D images and common genetic variants spread across the entire genome. We also attempted to independently replicate some of the findings from previous studies.
Dr. Seth Weinberg[/caption]
Seth M. Weinberg, PhD
Assistant Professor, Department of Oral Biology
Assistant Professor, Department of Anthropology
Director, CCDG Imaging and Morphometrics Lab
MedicalResearch.com: What is the background for this study?
Response: Scientists have long recognized that aspects of facial appearance have a genetic basis. This is most obvious when we look at the faces of people in the same family. It is also well known that mutations in certain genes can result in syndromes where the face is affected. However, very little is known about how specific genes influence the size and shape of normal human facial features. To date, only a handful of studies have looked at this question, and while these studies have reported several interesting results, only a small number of genes have so far been linked to normal variation in facial features. The primary goal of our study was to test for evidence of association between detailed facial measures derived from 3D images and common genetic variants spread across the entire genome. We also attempted to independently replicate some of the findings from previous studies.

Dr. Andrea M. Kriska PhD MS
Professor, Department of Epidemiology
Graduate School of Public Health
Pittsburgh, PA 15261
MedicalResearch.com: What is the background for this study?
Dr. Kriska: The Diabetes Prevention Program (DPP) was a well administered national research study primarily supported by the National Institutes of Health (NIDDK) that demonstrated that lifestyle intervention with weight loss and physical activity goals can prevent type 2 diabetes in diverse, high risk US adults. The importance of physical activity in preventing diabetes development in the DPP until now was thought to be due to its role in achieving weight loss and weight maintenance but activity was not considered a strong key factor alone.
The lifestyle group had a significantly greater increase in physical activity and decrease in weight than the other two groups. They also had a 58% decrease in diabetes incidence compared to the control group. The successful decrease in T2D held across all age, sex, baseline BMI and ethnicity/race subgroups.
Despite the fact that the lifestyle intervention was then offered to all participants, in the follow-up years, the lifestyle participants still maintained a lower cumulative diabetes incidence that could not be explained by differences in weight loss.
Dr. Donald Burke[/caption]
Donald S. Burke, M.D.
Dean of the University of Pittsburgh Graduate School of Public Health
Director of the University of Pittsburgh Center for Vaccine Research
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Burke: At the University of Pittsburgh we developed a unique method for detecting antibodies in the blood of patients in a proof-of-principle study that opens the door to development of simple diagnostic tests for diseases for which no microbial cause is known, including auto-immune diseases, cancers and other conditions.
We used a technique pioneered by co-author Thomas Kodadek, Ph.D., of the Scripps Research Institute, that synthesizes random molecular shapes called “peptoids” hooked onto microscopic plastic beads. The technique can produce millions of molecular shapes. The peptoids are not organic, but if they match to the corresponding shape on an antibody, that antibody will connect to them, allowing the scientist to pull out that bead and examine that peptoid and its corresponding antibody.
My team chemically generated a huge library of random molecular shapes. Then, using blood from HIV-infected patients and from non-infected people, we screened a million of these random molecular shapes to find the ones that bound only to antibodies present in the blood of HIV-infected patients, but not the healthy controls. No HIV proteins or structures were used to construct or select the peptoids, but the approach, nonetheless, successfully led to selection of the best molecular shapes to use in screening for HIV antibodies.
We then resynthesized that HIV-antibody-targeting peptoid in mass and tested it by screening hundreds of samples from the Multicenter AIDS Cohort Study (MACS), a confidential research study of the natural history of treated and untreated HIV/AIDS in men who have sex with men (supported by the National Institutes of Health). Study co-author Charles Rinaldo, Ph.D., chair of Pitt Public Health’s Department of Infectious Diseases and Microbiology and director of the Pittsburgh arm of the MACS, selected the samples, but blinded the testers to which samples were HIV-positive or -negative. The test distinguished between the samples of HIV-positive blood and HIV-negative blood with a high degree of accuracy.
Dr. Robert Ferris[/caption]
Robert L. Ferris, M.D., Ph.D.
Robert L. Ferris, M.D., Ph.D.
UPMC Endowed Professor and Vice-Chair
Associate Director for Translational Research
Co-Leader, Cancer Immunology Program
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Ferris: Investigators at the University of Pittsburgh Cancer Institute<http://upci.upmc.edu/> (UPCI) co-led CheckMate-141<https://clinicaltrials.gov/ct2/show/NCT02105636> a large, randomized international phase III clinical trial that enrolled 361 patients with recurrent or metastatic head and neck squamous cell carcinoma who had not responded to platinum-based chemotherapy, a rapidly progressing form of the disease with an especially poor prognosis. Patients were randomized to receive either nivolumab or a single type of standard chemotherapy until tumor progression was observed.
Nivolumab, which belongs to a class of drugs known as immunotherapeutics, enables the body’s immune system to destroy cancer cells. It currently is approved to treat certain types of cancers, including melanoma and lung cancer. The nivolumab group achieved better outcomes than the standard chemotherapy group by all accounts. After 12 months, 36 percent of the nivolumab group was alive, compared to just 17 percent of the standard chemotherapy group.
Nivolumab treatment also doubled the number of patients whose tumors shrunk, and the number whose disease had not progressed after six months of treatment. Importantly, these benefits were achieved with just one-third the rate of serious adverse events reported in the standard chemotherapy group. In addition, on average, patients receiving nivolumab reported that their quality of life remained stable or improved throughout the study, while those in the chemotherapy group reported a decline. The new trial was considered so successful that it was stopped early to allow patients in the comparison group to receive the new drug.
Dr. Laura Ferris[/caption]
MedicalResearch.com Interview with:
Laura Ferris, M.D., Ph.D.
Associate professor, Department of Dermatology
University of Pittsburgh School of Medicine and
Member of the Melanoma Program
University of Pittsburgh Cancer Institute
MedicalResearch.com: What is the background for this study?
Dr. Ferris: Rates of melanoma, the most dangerous form of skin cancer, are on the rise, and skin cancer screenings are one of the most important steps for early detection and treatment. Typically, patients receive skin checks by setting up an appointment with a dermatologist. UPMC instituted a new screening initiative, which was modeled after a promising German program, the goal being to improve the detection of melanomas by making it easier for patients to get screened during routine office visits with their primary care physicians (PCPs). PCPs completed training on how to recognize melanomas and were asked to offer annual screening during office visits to all patients aged 35 and older. In 2014, during the first year of the program, 15 percent of the 333,788 eligible UPMC patients were screened in this fashion.





















