The attached Pathways to Independence resubmission proposal (NIH application ID#1K99NR013176- 01), entitled `Transcriptomics in Traumatic Brain Injury: Relationship to Brain Oxygenation and Outcomes', is a career plan to develop research skills and training in the area of genomics, with a focus on brain oxygenation in severe traumatic brain injury (sTBI). As a recently appointed Assistant Professor (non- tenure track), this award will assist in the success of my ultimate career goals of becoming an independent nurse scientist by providing a solid foundation in genomics and also by developing an independent research program focused on improving neurological outcomes in TBI. This proposal is an natural extension of my previous education in neuroscience and nursing, my clinical nursing and research trials experience in sTBI, and my doctoral dissertation work, `Effect of Short Periods of Normobaric Hyperoxia on Local Brain Tissue Oxygenation & Cerebrospinal Fluid Oxidative Stress Markers in Severe Traumatic Brain Injury', which utilized innovative technology in our state-of-the art Neurotrauma ICU. Traumatic brain injury is a major societal concern affecting an estimated 2 million people per year, many of whom experience permanent neurological disabilities. Slowing the progression of secondary injury following a brain injury is the goal of the critical care team, and the use of innovative technology, such as brain oxygenation monitoring may assist in early diagnosis and intervention. A more extensive understanding of this physiology in relationship to genetic influences and responses may assist the intensive care team to advanced, individualization of care.
I aim to utilize this K99 grant support to develop additional expertise in three areas: 1) methodology of gene variance and expression; 2) physiology and pathophysiology of oxygen signaling within the sTBI population; 3) develop an appreciation for bioinformatic approaches in gene analyses. This proposal will be pivotal in expanding the knowledge base of genomics and brain oxygenation. With additional diagnostic techniques aimed at individualization of treatment care plans, this work will assist the neurointensive care nurse in improving neurological outcomes of sTBI patients. In collaboration with my primary mentor, Yvette Conley, PhD, a tenured Associate Professor of Nursing and Human Genetics, we have developed an impressive, interdisciplinary and multi-institutional advisory committee that includes established senior mentors and advisors with special expertise in 1) genomics (Dr. Conley), 2) oxygen physiology (Patrick Kochanek, MD, Professor and Vice Chairman of the Department of Critical Care Medicine), 3) traumatic brain injury (David Okonkwo, MD, PhD, Associate Professor of Neurosurgery), and 4) genomic bioinformatics (James Lyons-Weiler, PhD). We have also proposed a training plan that includes both formal and informal education and training that will provide a strong base of knowledge in key areas to pave the path for my independence. Formal training will consist of a combination of genomic intense workshops and didactic coursework in genomics and biostatistics, as well as informal training with Dr. Conley and Lyons-Weiler's genomic laboratories, survival skills and ethics workshops and frequent face-to- face mentoring with individual members of my advisory committee. Dissemination of the results of the K99 findings will be encouraged with attendance and presentations at National Conferences and a focus on development of publications and future R01 grant proposals. The primary aims of my K99 proposal are to identify global gene expression (Specific Aim 1) and assess genetic variance (Specific Aim 2) in the hypoxic-signaling pathway of sTBI adult, patients by training in the skills necessary to perform the laboratory and bioinformatic analyses. Blood and cerebrospinal fluid samples will be collected from sTBI patients, in conjunction with the mentors ongoing research projects to examine the genomics in relationship to brain oxygenation and neurological outcome. Brain oxygenation is an innovative bedside tool used by the neuroICU nurse to monitor brain oxygenation. Manipulation of oxygen delivery is a method used by the ICU team, including the neuroICU nurse to increase the oxygen delivery to the injured brain in instances of low brain oxygenation. These proposed research directives that further explain brain oxygen physiology and the genetic interplay may help determine the appropriate brain oxygenation target to individualize care of the sTBI patient. In the future, patients may have a genetic profile that dictates their therapy to optimize neurological recovery. The nurse is the optimal health care provider to assist the individual/family in the decision making process. I have the desire to develop collaborations in the field of nursing genomics and expand my skill set to enable me to pursue an independent research career in an intense academic setting. I have proposed an innovative research plan focusing on a disease process (sTBI) that is a societal concern. My developed interdisciplinary team of experts in the fields will provide mentoring that will poise me for success. Our proposed training plan includes formal and informal training and education that will supplement my knowledge in key areas for this work and my career development. Support through this Pathways to Independence award mechanism is a logical and essential next step in my development as a clinician-scientist in the emerging area of genomic approaches in sTBI research and nursing care.
Traumatic brain injury (TBI) is a major societal concern affecting 2 million people per year, many young, productive individuals who then experience permanent neurological disabilities. The examination of brain oxygenation in relationship to the genetic makeup and response of the TBI patients may assist in individualizing and improving the nursing care that we can provide. In addition, this innovative research may improve the neurological outcome and quality of life of the TBI patient and subsequently decrease familial and societal burdens.
|Jha, Ruchira Menka; Koleck, Theresa A; Puccio, Ava M et al. (2018) Regionally clustered ABCC8 polymorphisms in a prospective cohort predict cerebral oedema and outcome in severe traumatic brain injury. J Neurol Neurosurg Psychiatry 89:1152-1162|
|Jha, Ruchira M; Elmer, Jonathan; Zusman, Benjamin E et al. (2018) Intracranial Pressure Trajectories: A Novel Approach to Informing Severe Traumatic Brain Injury Phenotypes. Crit Care Med 46:1792-1802|
|Jha, Ruchira M; Puccio, Ava M; Okonkwo, David O et al. (2017) ABCC8 Single Nucleotide Polymorphisms are Associated with Cerebral Edema in Severe TBI. Neurocrit Care 26:213-224|