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Immune Checkpoint Blockade Induces Gut Microbiota Translocation That Augments Extraintestinal Anti-Tumor Immunity
Get PDFGut microbiota are critical for effective immune checkpoint blockade therapy (ICT) for cancer. The mechanisms by which gut microbiota augment extraintestinal anti-cancer immune responses, however, are largely unknown. Here, we find that ICT induces the translocation of specific endogenous gut microbiota into secondary lymphoid organs and subcutaneous melanoma tumors. Mechanistically, ICT induces lymph node remodeling and dendritic cell (DC) activation which facilitates the translocation of a selective subset of gut bacteria to extraintestinal tissues which promote optimal anti-tumor T-cell responses in both the tumor-draining lymph nodes (TDLN) and the primary tumor. Antibiotic treatment results in decreased gut microbiota translocation into MLN and TDLN, diminished DC and effector CD8+ T cell responses, and attenuated response to ICT. Our findings illuminate a key mechanism by which gut microbiota promote extraintestinal anti-cancer immunity
Creation of a Path
Get PDFThe author submitted this entry in the Open Verse Poetry category (Amateur division) for the 2023 On My Own Time (OMOT) Art Show.The sidewalks are sporadic, unkempt, and inconsistent where I live. Yet in the grass between the missing concrete, I often notice a path made by years of collaborative footsteps. The idea of creating one's own physical or mental path, with the help of the community, led me to this poem
The Role of Incarceration in Treatment-Seeking Veterans with PTSD: Evaluating Differences in Trauma Symptoms, Suicidality, and Substance Use
Get PDFVeterans are an at-risk population with increased chances of exposure to trauma, mental health diagnoses, substance use, and suicidality. Individuals who have been incarcerated demonstrate similar increased risks. As such, when a Veteran also has a history of incarceration, these risks may be exacerbated. It is posited the rate of PTSD among Veterans is 11-20% (National Center of PTSD, 2019). Additionally, it is estimated over 120,000 Veterans are currently incarcerated, with as many as 67% having a mental illness or substance use disorder (Finlay et al., 2017; Bronson et al., 2015). This study aimed to examine how a history of incarceration may impact trauma symptoms in Veterans, and how this differs when compared to Veterans without an incarceration history. The data did not support overall differences between these two groups; however, exploratory analyses suggest potential areas of future directions. Exploratory analyses suggest potential differences in PTSD symptomology, specifically increased endorsement of Cluster C / avoidance among Veterans with PTSD, and increased risk taking among Veterans with PTSD and an incarceration history. Results also suggested higher rates of substance use treatment among Veterans with PTSD and an incarceration history. Lastly, analyses suggest higher endorsement of feeling "tense and keyed up" among Veterans with PTSD. No differences were found between groups in areas of PTSD severity, number of endorsed trauma events, suicidality, or adverse childhood events
Autosomal dominant tubulointerstitial kidney disease
Get PDFDetailed formal protocol with illustrations and extensive bibliography.A recording of the protocol presentation is available on UT Southwestern's Mediasite. Note: Access to the video is restricted to authorized UT Southwestern users only.UT Southwestern--Internal Medicin
You Were There
Get PDFThe author submitted this entry in the Open Verse Poetry category (Amateur division) for the 2023 On My Own Time (OMOT) Art Show.As a Nurse for 40 plus years, in an era where we have more options available for careers as a woman, I wrote this when the question was posed "Why did you become a Nurse?". A prose that reflects my own experience, and knowledge that I make an impact with my purpose. I wrote this in 2010, prior to the Covid Pandemic
Genomics of Butterflies
Get PDFThe success of next generation sequencing technologies enabled us to study biological questions by comparative genomics of a large group of organisms. We developed methods to sequence and comparatively analyze genomes of butterflies and address general questions of molecular evolution and connection between genotype and phenotype. First, we study mimetic convergence and divergence on a phylogenetic group of butterflies revealing many instances of rapid phenotypic changes between close relatives. Second, we sequence and analyze the genome of a gypsy moth, a notorious pest accidentally introduced to American from Europe and hypothesize about the differences in flight capacity of different moth populations. Third, we study speciation in Texas butterflies and uncover general criteria and molecular mechanisms for speciation across central Texas suture zone. Finally, we obtain whole genome shotgun sequences of all 845 butterfly species recorded from the United States and Canada, and learn about the patterns of their speciation and rapid diversification, connecting them to possible molecular mechanisms such as gene exchange through hybridization. As a result, we see that butterflies are a promising group of model organisms to connect molecular and organismal biology by means of genomics, ripe in future discoveries
Sensory Neurogenesis and the Role of PRDM12 in Nociceptor Development and Function
Get PDFNociceptors are a set of peripheral neurons responsible for the detection of noxious stimuli. They function to alert us to the presence of potentially damaging internal and environmental threats, thereby playing an important role in allowing us to react and avoid danger. Unfortunately, for over 30% of the population, the sense of pain derived from nociception becomes maladaptive, leading to chronic painful conditions which carry an estimated economic burden of over USD 600 billion. While opioids are the current mainstay analgesic medication, they have a vast array of side effects, including risk of overdose and death, which makes their use in treatment of chronic conditions far from ideal. Recently, studies of genetic mutations leading to congenital insensitivity to pain (CIP) have provided a springboard for the development of novel analgesics targeting nociceptor function in the periphery. The identification of additional such mutations in the gene Prdm12 raised questions about processes inherent to nociceptor development and sensory neurogenesis as a whole, and what function this gene plays in mature primary afferent neurons.
Over the course of my dissertation work I sought to address some of these questions by studying the development of nociceptive neurons in mice, and the effect of Prdm12-knockout on pain sensation. To establish a framework for sensory neuronal development, I first completed a birthdating study using a thymidine analog to permanently label cells undergoing their final mitotic divisions and identify them at later timepoints. With this, I show that there is no temporal difference in the birth rates of different nociceptor subtypes, but that most are born after touch and proprioceptive neurons. Next, using multiple models to knockout Prdm12 at various timepoints ranging from conception to adulthood, I then provide evidence that this is a key transcription factor for specification of the nociceptor population, but that its function likely changes over time. Loss of Prdm12 during development causes defects in nociception, but no behavioral phenotype was readily discernible following adult knockout. Instead, I show that Prdm12 appears to regulate a population of stem cell-like neurons, with an as-yet unknown role in dorsal root ganglia. Altogether my work highlights the role of Prdm12 in nociceptor development and lays the groundwork for additional studies to investigate the clinical relevance of this gene
Automated Treatment Planning in High Dose-Rate Brachytherapy for Cervical Cancer
Get PDFStandard care of cervical cancer is chemoradiation therapy followed by a boost to the cervix tumor site with High-dose-rate brachytherapy (HDRBT). HDRBT is a procedure that involves the insertion of radioactive sources into the tumorous area to ablate the cancer. Treatment planning for the procedure is typically performed on the day of treatment. The complex treatment planning process has led to issues such as prolonged treatment planning time and suboptimal plan quality. This dissertation reports systematic studies to improve treatment planning for HDRBT of cervical cancer. After a brief overview in Chapter 1, Chapter 2 will analyze the problems of sub-optimal plan quality and time management in the treatment planning workflow at our institution. In Chapter 3, developments on computational modules for automatic organ segmentation will be presented. Current clinical practice primarily relies on manual organ segmentation, but we have developed deep-learning models to segment the bladder, rectum, and sigmoid colon automatically, organs of particular importance for cervical cancer HDRBT. In Chapter 4, I present integration of the organ segmentation modules and other modules into the AutoBrachy system for clinical use to automate the planning process. Chapter 5 presents a deep-learning based method that can predict the physician's preference for a patient-specific treatment plan as defined by EQD2 to the bladder, rectum, sigmoid, and CTV D90. This method will serve as a guide in the future to automatically create patient-specific physician preferred treatment plans. Chapter 6 reports the study analyzing benefits from the use of joint intracavitary and interstitial HDRBT. Finally, Chapter 7 concludes the dissertation with discussions and future work
A Fifth of the World
Get PDFThe author submitted this entry in the Fictional Short Story category (Amateur division) for the 2023 On My Own Time (OMOT) Art Show.When I learned about neural remodeling following limb loss, I immediately grew curious about what other types of remodeling could occur. If one lost all but one of their senses, I wondered, how strong would the connections be to that particular modality? What would a world where individuals only had one sense or a mixture of two to three look like? Smell like? Feel, sound, and taste like
Posttrial responsibilities to participants in neural device research
Get PDFTuesday, October 10, 2023; noon to 1 p.m. (Central Time); Room NB2.100A or via Zoom. "Posttrial Responsibilities to Participants in Neural Device Research". Saskia Hendriks, M.D., Ph.D., Bioethicist, Department of Bioethics, Clinical Center, National Institutes of Health and Neuroethics Consultant, Neuroethics Program, National Institute of Neurological Disorders and Stroke.Developing new therapeutic devices may reduce the high burden of neurological and psychiatric disorders. In trials in which participants benefit from the device, or explantation is risky, device-related care for participants after the trial ends is a major ethical and practical challenge. Most patients who benefit from a device want to keep it. However, they may need among others, follow-up visits, replacement hardware, and software updates to maintain their benefits and reduce risks. Most posttrial needs are currently inconsistently met, which can lead to major consequences for patients. In some cases, patients have been left with a defunct implant. While some guidance exists for pharmaceuticals, specific guidance or best practices for device trials are lacking. Do researchers, funders, and industry-partners have responsibilities to facilitate posttrial care for research participants?UT Southwestern--Program in Ethic