University Of Tx Md Anderson Can Ctr

NIH Research Projects · FY 2025 · 2002-04

This resource provides unique primate reagents and services not available commercially in support of NIH funded investigators using nonhuman primates (NHP) as pre-clinical models for vaccine efficacy and immunotherapies. State of the art investigations of immune responses related to human infectious diseases, autoimmune diseases, organ and cell allogeneic and xenogeneic transplantation models or immunization procedures that use NHP models increasingly include the use of recombinant cytokines, chemokines, growth factors or immunomodulatory ligands in vivo. While the close evolutionary relationship between human and nonhuman primates generally provides cross reactivity between most human recombinant factors when used with NHP cells, differences in affinity/bioactivity have been noted. More important however, most NHP molecules are not identical to human homologues, often leading to the development of neutralizing antibody responses to the xenogeneic molecule in vivo, markedly restricting the repeated and most optimal in vivo use of select immunomodulators in these models. The ready availability of standardized purified recombinant NHP reagents has largely alleviated this limitation and allowed investigators to address seminal questions using NHP during the past 15 years of funding. Of note, while some commercial companies have started to produce a limited set of NHP cytokines, the costs charged by these companies is generally well beyond the budget of most NIH research awards, further validating the continuous need for this Resource. In addition, testing of in vivo administration of these reagents has markedly revised the clinical administration schedule, leading to more tolerable and efficacious dosing. Last but not least, we propose to leverage the strengths available at NIRC in imaging NHP technologies, to generate novel antibody based ligands for imaging technologies that are increasingly used in support of scientific explorations. Thus, this application requests continued support for allowing this Resource to provide NHP factors, in DNA and protein form. Specifically, the resource will perform the following: 1. Continuation and expansion of preparation, optimization, testing and distribution of NHP cytokines/chemokines and soluble receptors in protein and recombinant DNA expression vectors. 2. Generation and optimization of primate specific PET and fluorescent probes to be used in vivo and 3. Collaboration with the NIH Nonhuman Primate Immune Resource led Dr. D Magnani at UMass in the generation of noncommercially available monoclonal antibodies to NHP cytokines.

NIH Research Projects · FY 2025 · 2000-09

Although knowledge of cancer biology in the laboratory has increased exponentially in recent years, progress in cancer treatment in the clinic has been more gradual. To accelerate progress in the clinic, a larger group of exceptional clinician-investigators is needed to perform patient-oriented, hypothesis-driven therapeutic translational research. The MD Anderson (MDACC) K12 Paul Calabresi Program in Clinical Oncology has taken advantage of an extraordinary environment for clinical and translational research to help fill this need. MDACC brings together 2,014 faculty and over 40,000 new patients each year with a well-developed infrastructure for clinical and laboratory research and novel ideas that are supported by more than 300 NCI grants. For eight decades, MDACC investigators have made important contributions to clinical cancer research. Since the inception of the MDACC K12 Program in 2000, 40 junior faculty investigators have been trained in patient-based translational research with the Program’s support. Of the 35 graduates, 31 (89%) remain in academia and 13 have made discoveries that have changed cancer care. Collectively, MDACC Calabresi Scholars have authored over 6,300 peer-reviewed publications and have an average h-index of 39.83 (reported by Scopus). They have competed successfully for more than $35M in grants and contracts. Over the next five years, faculty supported by this award will conduct hypothesis-driven clinical trials and will have the opportunity to earn an M.S. or Ph.D. in a newly-chartered program in Clinical and Translational Science. They will participate in the monthly “Master Class” and the annual “Calabresi K Symposium”. Their Individualized Training Plans will include didactic classes, clinical trials, publications, grant applications, and long-range planning. Each Calabresi Scholar is guided by a clinical mentor and a translational mentor chosen from more than 45 subject matter experts in clinical, laboratory, and translational research. Particular emphasis will be placed on rigorous program evaluation and scholar progress. Our overall goal is to identify and develop careers of leaders who are needed to move an increasing number of new drugs and strategies from the laboratory to the clinic and to bring insights, images, data, and tissue from the clinic to the laboratory, accelerating the development of more effective, less toxic personalized therapy. Funds are requested to include five junior faculty not only from MDACC, but also from UT Health in Houston.

NIH Research Projects · FY 2025 · 2000-05

The Great Lakes New England Clinical Validation Center (GLNE CVC), a Clinical Validation Consortium component of the Early Detection Research Network (EDRN) is a highly collaborative group of investigators whose aims to validate biomarkers for the early detection and risk assessment of cancers of the gastrointestinal tract. In this fifth competitive application, the GLNE continues to test the overall hypothesis that a panel of circulating and stool based biomarkers will increase the adherence to colorectal screening and in doing so reduce mortality caused by colorectal cancers. Based on the rising incidence of colorectal cancer (CRC) among young adults in the US, and the low compliance overall with colorectal cancer screening, increased emphasis is placed on assays which promote better compliance with screening in all populations. The GLNE also proposes to continue its ongoing support of EDRN discovery priorities. We propose to address the following aims: (1) Primary Aim To expand and renew the archive of appropriately preserved stool, serum, plasma, urine, tissue and DNA biospecimens to be used by EDRN investigators for current and future validation and biomarker discovery research across a wide range of individuals. This will allow assessment of the utility of individual stool-based, and serum-based biomarkers and biomarker panels for discriminating between individuals without neoplasia (subjects both at average and higher risk for developing colon cancer), and those with colon cancer or screen-relevant neoplasia (cancer plus advanced adenoma), and construction of panels of markers to discriminate between these groups. (2) To perform validation trials of promising biomarkers discovered by EDRN investigators, external collaborating institutions and collaborating EDRN industrial partners for the early detection of colorectal neoplasia. In this context we propose to (a) to clinically validate (via a methods comparison study) the performance of a point-of-care blood- based biomarker panel with the testing of serum/plasma samples obtained in a variety of settings to insure the generalizability of the assay (b) to clinically validate an established 4-plex stool protein panel for early diagnosis of CRC. (3) To follow prospectively subjects enrolled in an established prospective Phase 2 validation trial to identify pre-diagnostic specimens which may be used to develop predictive markers.

NIH Research Projects · FY 2025 · 1997-04

PROJECT SUMMARY: OVERALL COMPONENT This application is a competing renewal of the “Squirrel Monkey Breeding and Research Resource” (SMBRR) P40 OD010938 which has received continuous NIH grant support since 1980. The SMBRR is the only national research resource of squirrel monkeys available to NIH grantees, intramural research programs of federal agencies including the FDA, NSF, and the NIH, and other sponsors of biomedical research (private foundations, pharmaceutical companies, and contract research organizations). Because Bolivian squirrel monkeys are no longer available from source countries, and there are no other breeding colonies of pedigreed squirrel monkeys available for biomedical research, the SMBRR is a unique research resource that cannot be duplicated or replaced. The scarcity of squirrel monkeys, difficulties associated with captive breeding, as well as the challenges associated with their care and use in research, all contribute to the need for this nationalresearch resource. The SMBRR has integrated multiple disciplines into a program designed to meet the needs of investigators who utilize its resources. In the upcoming years, the SMBRR will continue to improve the resources it provides and continue to add new information about the biology and research value of squirrel monkeys. Squirrel monkeys continue to be an important animal model in neuroscience research, drug addiction research, malaria vaccine research, and fundamental evolutionary biology. Over the next five years,the SMBRR will focus on refining the animals and related resources to meet the needs of the scientific community. The aims of the Resource Core Component address our continued commitment to meeting the needs of the research community for access to squirrel monkeys and information about using squirrel monkeysin research. We will explore the causes of perinatal mortality in a retrospective epidemiology study as well as the potential role of different genes. We will expand our biobanking program to prioritize collection of frozen and formalin-fixed tissued for use in molecular biological and gene expression studies (both bulk and single nuclei approaches). The Applied Component research projects focus on basic research projects that will enhance to use of the SMBRR and provide data on best practices and uses of different anesthetics on brain and behavior. The Curation and Informatics Component is designed to simplify access to SMBRR materials by the scientific community and to facilitate accurate documentation of its use. The overall goals of the SMBRR are to provide a national research resource of squirrel monkeys; provide squirrel monkey derived biological materials; provide education and training opportunities to scientists wishing to workwith squirrel monkeys, colony managers, and animal caregivers; and provide investigators with facilities and expertise to conduct studies using squirrel monkeys.

NIH Research Projects · FY 2025 · 1996-08

MD Anderson Cancer Center is a comprehensive cancer center established within the University of Texas System in 1941. In 2017, the institution welcomed Peter Pisters, MD, as its fifth full-time president and PI of the CCSG. The mission of MD Anderson is to eliminate cancer in Texas, the nation and the world through outstanding programs that integrate patient care, research and prevention, and through education for undergraduate and graduate students, trainees, professionals, employees and the public. MD Anderson is dedicated wholly to the study of cancer involving a continuum of basic, clinical and population-based investigation, with an emphasis on multidisciplinary translational research. MD Anderson employed more than 19,530 people in FY17, including 1,743 faculty members, of whom 705 (40%) are CCSG program members. More than 137,000 people sought care at MD Anderson in FY17 of whom 20,839 were newly diagnosed cancer patients. Annual citations in Web of Science have increased 23% from 3,260 in 2013, to 4,009 in 2017, including 686 (17%) articles in journals with an impact factor >10, and 244 (6%) articles in journals with an impact factor >20. The total research budget increased 26% from $671M in 2013 to $844M in 2017. Direct cost NCI research grant support, excluding training grants and the CCSG, has increased 34%, from $67M in 2013 to $90M in 2018, with the largest number of NCI grants for any institution (>200), including 6 SPOREs, 4 P01s and 35 U awards. Research Programs have been reduced to 16 and support is requested for 14 shared resources. Since the last CCSG renewal, research has been strengthened with recruitment of 97 tenured and tenure track faculty, of whom 18 are supported by recruitment awards from CPRIT totaling $63M. Team science has been enhanced through institutional support of the MD Anderson’s Moon Shots ($383M), focused on reducing mortality from 13 major cancers through multi-disciplinary efforts that build on research emerging from the CCSG programs. In FY17, 10,283 participants were enrolled in 1,108 interventional clinical research protocols, of which 936 were treatment (therapeutic) studies that accrued 6,271 subjects. Over the past decade MD Anderson investigators have contributed to the clinical evaluation of 72 of 130 FDA oncology drug approvals, either as a new entity or for a new indication, with 41 of these approvals since the last CCSG renewal. In addition to the main hospital, Houston Area Locations provide prospective, multidisciplinary care and supportive services, with an increasing emphasis on access to clinical trials including national studies. Cancer prevention and survivorship is a priority for MD Anderson with an emphasis on molecular epidemiology, behavioral science, clinical cancer prevention and early detection research to reduce the burden of cancer within Texas and worldwide.

NIH Research Projects · FY 2024 · 1994-09

Project Abstract The MD Anderson Cancer Center (MDACC) T32 Research Training in Academic Medical Oncology Program capitalizes on the availability of highly qualified fellows from within the MDACC Hematology/Medical Oncology fellowship program to provide two years of academic research training to selected first-year fellows who have demonstrated strong commitment to a career as a physician scientist or translational clinical investigator in Medical Oncology. The T32 training program is thus a “program within a program,” but has a separate and distinct organizational and administrative structure with the following specific objectives: 1) To provide and integrate robust didactic, clinical, and lab-based research components within a structured training program focused on the conduct of innovative medical oncology-based research; 2) To prepare trainees for successful careers in academic medicine as physician scientists and clinician investigators focused on novel discoveries and their clinical translation to improve the outcomes of patients with cancer; and 3) To provide a broad range of structured career development opportunities, including the development of skills necessary to obtain peer- reviewed funding to support each trainees’ transition to a faculty position in academic medical oncology. Our T32 program involves new leadership with Dr. Michael Davies and Dr. Katy Rezvani as Co-PIs, both accomplished investigators with long-term commitments to education and established track records in successfully mentoring trainees. The program involves an expanded panel of highly accomplished and nationally/internationally recognized program faculty (including Drs. James Allison, Ron DePinho, Helen Piwnica-Worms, Patrick Hwu, John Heymach and others), and provides a broad range of training opportunities that fully exploits the unique research environment at MDACC. These opportunities include participation in new and rapidly developing multidisciplinary research programs in genomic medicine, systems biology, targeted drug development for personalized cancer therapy, and cancer immunotherapy, including cellular immune therapies and hematopoietic transplantation. The program is also enhanced by the extensive programmatic and shared resources of MD Anderson as an NCI-designated Comprehensive Cancer Center. The T32 program has been highly successful in producing academic medical oncologists who have made a major impact on the field, with 88% of the T32 graduates in the past ten years successfully obtaining academic faculty appointments. This renewal application includes additional plans for career development and mentorship to meet the challenges of an increasingly competitive landscape for young investigators. Finally, our application includes an invigorated program governance structure to further our development of the next generation of leaders in clinical, translational, and laboratory-based oncology research.

NIH Research Projects · FY 2026 · 1994-05

With the rapid progress in cancer biology, there is a great need to train academic surgical oncologists who can not only deliver state-of-the art surgical care, but can also lead multidisciplinary teams and research programs leveraging molecular oncology, immunology, and other emerging fields. To address the national shortage of surgical investigators focused on surgical oncology, the Department of Surgical Oncology at The University of Texas MD Anderson Cancer Center has dedicated its T32 training program to producing academic surgical oncologists. The long-term objective is to train surgical residents and surgical oncology fellows in the essential research skills necessary to be productive independent surgical investigators in clinical, translational, and laboratory-based oncology research and to become leaders in oncology. Training is offered to eight postdoctoral MD or MD PhD fellows either during a 24-month hiatus from general surgery residency training (‘research fellows’) or during a three-year combined clinical/research fellowship in surgical oncology (‘clinical/research fellows’) that begins after general surgery residency. Our T32 training program has been highly successful in achieving its goals and is now entering its 35th year. Upon completion of residency, most of our T32 research fellows either started fellowship training, or accepted academic surgical positions. Upon completion of surgical oncology fellowship training, 100% of our T32 clinical/research fellows entered academic Surgical Oncology positions. Our T32 program provides research opportunities in a broad range of basic oncologic disciplines, in one of three training tracks; (a) basic and translational research, (b) quality, clinical effectiveness and outcomes, and (c) clinical trials and biomarkers. This academic training program allows us to train surgeons with a diverse set of unique skills, increasing the likelihood of trainees obtaining an academic position upon completion of training. Training in biostatistics, responsible conduct of research, reproducibility, and a rich array of seminars and graduate courses available are integral to the T32 program. The T32 program faculty includes a multidisciplinary faculty pool, including established surgical investigators, junior faculty, department chairs, medical and radiation oncologists as well as basic-science researchers, all of whom have peer-reviewed grant support. MD Anderson is a leading NCI-designated Comprehensive Cancer Center that provides trainees access to unique resources and our location in the Texas Medical Center provides our trainees potential collaborators at six academic institutions. Thus, the University of Texas MD Anderson Cancer Center is a highly stimulating environment for future leaders in academic surgical oncology.

NIH Research Projects · FY 2026 · 1992-07

Since 1992, MD Anderson Cancer Prevention Education: Student Research Experiences has provided short-term, intensive training in cancer prevention research and education to encourage students to pursue careers in this vital field. The Program recruits undergraduate, graduate, and health professional students from the basic biomedical sciences, biostatistics, epidemiology, genetics, behavioral and social sciences, nursing, medicine, pharmacy, and related public health disciplines. Beginning with 10 positions in 1992 and increasing over time, the Program now supports 25 positions annually. Other than pandemic shutdown-year 2020, to date, all positions have been filled annually. The Advisory Committee reviews and selects the students based on the merit of their academic performance, educational objectives, and research interests. The Specific Aims are to recruit nationally and train 25 high-performing students for 10-week positions annually, using effective national outreach strategies; to cultivate and support our pool of mentors; to provide a superlative mentored research training experience in a variety of cancer prevention disciplines; to provide career and professional skills development and research ethics; to strengthen students’ preparation for careers in science through structured engagement in research and scholarly activities; and to rigorously evaluate the Program’s value and effectiveness, tracking students’ career trajectories long-term. The Program centers on mentored research designed by faculty with clear student learning objectives. Curriculum components include instruction in cancer prevention and control principles, exposure to career pathways in the field, and professional development focused on career decision-making and navigation. Building on a history of successful educational innovation, the current renewal will refine the curriculum to deepen engagement with cancer prevention research and improve strategies that support student learning and career persistence. These include activities that promote self-awareness and equip students to manage challenges such as imposter feelings and fixed mindset beliefs – factors that may hinder academic and professional growth. Linking personal values and themes in research and cancer prevention accumulated over 10 weeks with the value of pursuing careers in the field will serve as a way to extend and intensify interest in such careers after the end of the Program. Program success is reflected in the development of student-authored research products, publications, and the growing number of alumni who have advanced from graduate training into independent research and leadership roles in cancer prevention.

NIH Research Projects · FY 2026 · 1988-07

Abstract The p53 tumor suppressor is a DNA damage/stress response protein that functions as a transcription factor to regulate a large repertoire of genes that prevent proliferation of damaged cells via initiation of cell cycle arrest and senescent programs or via apoptosis and other mechanisms of cell death. However, the molecular, morphological, and physiological consequences of this transcriptional program remain poorly understood in vivo. We have defined the physiological p53 transcriptional program using the mouse as a model system. Global p53 activation causes anomalies in the pancreas (an acinar to ductal metaplasia), intestine (crypt atrophy) and kidney (dilated tubules), and directly activates hundreds of genes many in a tissue-specific manner. Seven genes, however, are universally expressed in the five tissues (pancreas, intestine, kidney, ovary, heart) examined and represent a pan-tissue p53 transcriptional signature which includes Mdm2 (which encodes a potent p53 inhibitor) but not p21 (a cell cycle inhibitor and first identified p53 target gene). The pan-tissue p53 transcriptional signature includes three other genes with central functions in cell survival or cell death for which little is known. Eda2r is a transmembrane receptor and member of the TNF family with the ability to induce apoptosis. Significantly reduced expression of EDA2R is observed in mutant p53 breast, colorectal, and lung cancers and in pancreatic ductal adenocarcinoma and glioblastoma. Gtse1 encodes a cytoplasmic protein that migrates to the nucleus upon DNA damage, and binds and inhibits p53 activity in cells in culture. A review of cancer sequencing data indicates that amplification of GTSE1 is mutually exclusive with TP53 alterations in angiosarcomas further implicating it as an inhibitor of p53 function. Polκ is an error prone DNA polymerase that allows replication of damaged DNA and ensures cell survival, but contributes to an increased mutation burden. We hypothesize that these three transcriptional targets are key effectors of the p53 pathway and functionally contribute to ensure cell survival (via cell cycle arrest or senescence) or initiate cell death. In addition, two of these effectors have opposing properties: Eda2r induces apoptosis, while Gtse1 inhibits p53 activity and ensures cell survival. Single cell analysis in the pancreas upon p53 activation, either by deletion of Mdm2 or inflammation, will be performed to understand the cell-specific and dynamic nature of the p53 transcriptional program. The specific aims are: 1) to determine the roles of Eda2r in p53-dependent processes in vivo; 2) To determine the importance of Gtse1 in inhibiting p53 activity in vivo; 3) To determine the functional significance of p53 regulation of Polκ in homeostasis, inflammation and cancer; and 4) To determine the specificity of the p53 response using single cell analyses of the pancreas. A deep fundamental knowledge of the physiological p53 transcriptional program and individual cellular outcomes is essential to maximize the efficacy of p53 activation therapies and may reveal novel therapeutic strategies.