Dr. Jordan Orange has been selected to receive a 2017 Michael E. DeBakey, M.D., Excellence in Research Award, a prestigious honor given annually to Baylor College of Medicine faculty who have made the most significant published scientific contribution to clinical or basic biomedical research during the past three years.
Orange’s peers – Drs. Emily Mace, Lisa Forbes and Tiphanie Vogel – nominated him for the award in honor of his work as a distinguished pediatrician-scientist who has made seminal contributions to the fields of clinical immunology, basic immunology and cell biology.
Specifically, they highlighted three papers that represent the breadth, caliber and recent impact of Orange’s work as chief of the Section of Immunology, Allergy and Rheumatology and director of the Center for Human Immunobiology. These papers were published in Nature Genetics, the Journal of Clinical Investigation and the Journal of Cell Biology and are described in greater detail below.
“Dr. Orange orchestrates a vibrant and successful clinical and basic research program applying cutting-edge cell biology to questions of important clinical relevance,” Mace said. “In addition to being a pioneer in the field of NK cell deficiency and an international authority in the study and treatment of primary immunodeficiency, he is also a world’s expert in the field of highly quantitative imaging, including super-resolution and total internal reflection microscopy.”
Mace added that Orange’s scientific accomplishments are paralleled only by his success as a leader and mentor.
“His scientific vision and innovation are combined with tireless dedication to both teaching and learning,” she said. “We all are honored to count him as a colleague.”
Orange will be presented with the DeBakey, M.D., Excellence in Research Award on May 15. To learn more about the award, click here. To learn more about the scientific research that garnered Orange the DeBakey award, see below.
Nature Genetics – Through collaboration with the Baylor Hopkins Center for Mendelian Genomics, Orange has become a leader in the discovery of novel monogenic causes of primary immunodeficiency. The discovery of COPA syndrome (Watkin et al., Nature Genetics 2015) was the result of a multi-institute collaboration led by Orange. This rare, autosomal dominant autoimmune syndrome leads to arthritis and interstitial lung disease and was identified through whole exome sequencing of affected patients and their unaffected family members. This genetic discovery was validated in Orange’s laboratory by identifying the mechanism of disease through modeling of the impacted pathway. This work was also recognized with the Lee C. Howley Sr. prize for the most outstanding paper of the year by the Arthritis Foundation in 2015.
Journal of Clinical Investigation – NK cells are innate lymphocytes that eliminate infected or diseased cells. The field of primary NK cell deficiency (NKD) is one in which Orange has been a pioneer; he penned one of the first descriptions of NKD in 2003. While rare, NKD is severe and frequently fatal. To date, four monogenic causes of isolated NKD have been published, two of these from Orange’s group. Most recently, Orange led an international team that discovered biallelic mutations in the transcription factor IRF8 are a novel cause of NKD. This paper, published in the Journal of Clinical Investigation in 2017 (Mace et al.), ended a decade-long quest to solve the original published case of NKD. Again, modeling of patient mutations in the Orange laboratory using cutting-edge cell biology revealed the mechanism of impaired NK cell development in a cohort of patients from unrelated families.
Cell Biology – As NK cells lie at the heart of Orange’s research, it is not surprising that understanding NK cell function has been a cornerstone of his basic science program. He has led the field of NK cell biology by using highly quantitative microscopy and image analysis to deeply probe their function. In the January 2017 issue of the Journal of Cell Biology, Hsu et al. describe the purpose of NK cell lytic granule convergence, a mechanism by which NK cells direct their potent cytolytic machinery to prevent damage to bystander cells. This finding, which has important clinical implications for the field of immunotherapy, featured the application of novel technology to mimic an NK cell microenvironment. This work was showcased on the cover of the journal and merited an editorial from the well-known cell biologist Dr. Ira Mellman, as well as a feature on the journal’s weekly podcast.