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Principal Investigator: Kevin Thomas Nead
Organization: UNIVERSITY OF TX MD ANDERSON CAN CTR
Fiscal Year: 2024
Award: $258,561
Funding agency: National Cancer Institute
PROJECT SUMMARY
Studies in healthy individuals have shown that acquired DNA mutations are surprisingly common in normal-
appearing tissues. Clonal hematopoiesis (CH) mutations are acquired mutations in the blood present in the
majority of older individuals. CH mutations are also frequent among individuals with solid malignancy; are
associated with past receipt of oncologic therapy, in particular radiation therapy; and are associated with worse
overall survival. This project will address key knowledge gaps by investigating whether CH mutations are
associated with adverse oncologic treatment toxicity and outcomes in patients with solid malignancy (Aim 1),
how oncologic therapy impacts the frequency and characteristics of CH mutations in patients with solid
malignancy (Aim 2), and whether there are actionable intermediary biomarkers of adverse outcomes among
individuals with CH mutations (Aim 3). We will address these aims by undertaking targeted DNA sequencing
using existing biospecimens from prospective cohorts of patients undergoing oncologic therapy for solid
malignancy (Aims 1 and 2) and using existing clinical and genetic data from a large prospective biobank (Aim
3). Our approach leverages unique patient resources and novel methodology. Completion of these aims will
provide key insight regarding the importance of CH mutations in patients with solid malignancy and guide
future investigations to determine whether knowledge of CH mutations can improve cancer care. The
applicant, Dr. Kevin T. Nead, MD, MPhil, is an assistant professor in epidemiology and radiation oncology at
MD Anderson Cancer Center. This study is in line with Dr. Nead’s long-term career goal to become an
independent, R01 funded investigator studying the use of inherited and acquired patient-level genetic data to
improve cancer prevention and treatment paradigms. The overall career development objectives of Dr. Nead’s
proposal are to 1) expand his knowledge and expertise in genetics/genomics, bioinformatics, somatic mutation
analysis, and study design; 2) complete an interdisciplinary research plan and establish a published body of
work on acquired mutations in normal tissues and oncology care; and 3) build a platform for his successful
transition to an independent investigator. During the award period Dr. Nead will devote at least 75% of his
effort to the proposed project and career development activities. Dr. Paul Scheet, the candidate’s primary
mentor, is chair of the Department of Epidemiology, an international expert in the study of acquired mutations
in normal tissue, and has received multiple awards for the quality of his mentorship and teaching. Dr. Nead will
also benefit from the rich training environment and outstanding resources and mentorship available at MD
Anderson Cancer Center for the proposed project. Completion of the proposed research and career
development plan will give Dr. Nead the necessary knowledge and skills to transition to independence and to
pursue an impactful career improving cancer prevention and care.
Terms: <Aberrant Chromosome><Address><Adverse Experience><Adverse event><Award><Bio-Informatics><Bioinformatics><Biological Markers><Blood><Blood Reticuloendothelial System><Blood Sample><Blood specimen><Body Tissues><Breast><Cancer Center><Cancer Treatment><Cancers><Cardiovascular Diseases><Caring><Cell Body><Cells><Characteristics><Chemotherapy and Radiation><Chemotherapy and/or radiation><Chest><Chromosomal Aberrations><Chromosomal Abnormalities><Chromosomal Alterations><Chromosome Aberrations><Chromosome Alterations><Chromosome Anomalies><Chromosome abnormality><Clinical><Clinical Data><Clinical Markers><Clinical Research><Clinical Study><Collection><Cytogenetic Aberrations><Cytogenetic Abnormalities><DNA Alteration><DNA Sequence Alteration><DNA mutation><DNA seq><DNA sequencing><DNAseq><Data><Data Set><Department chair><Development Plans><Development and Research><Disease><Disorder><Education><Educational aspects><Educational process of instructing><Electronic Health Record><Eligibility><Eligibility Determination><Environment><Environmental genotoxicant><Epidemiology><Event><Evolution><Exercise stress test><Exposure to><Frequencies><Funding><Future><Genetic><Genetic Alteration><Genetic Change><Genetic defect><Genetic mutation><Genomics><Genotype><Goals><Health><Hematopoiesis><Hematopoietic Cellular Control Mechanisms><Hereditary><Individual><Inherited><Interdisciplinary Research><Interdisciplinary Study><International><Investigation><Investigators><Knowledge><Link><Lung Diseases><Malignant Neoplasm Therapy><Malignant Neoplasm Treatment><Malignant Neoplasms><Malignant Tumor><Mentors><Mentorship><Methodology><Methods><Modeling><Multidisciplinary Collaboration><Multidisciplinary Research><Mutate><Mutation><Mutation Analysis><Normal Tissue><Normal tissue morphology><Older Population><Oncology><Oncology Cancer><Outcome><Patient Care><Patient Care Delivery><Patients><Physicians><Population><Position><Positioning Attribute><Prevention><Process><Proliferating><Prospective cohort><Protocol Screening><Publishing><Pulmonary Diseases><Pulmonary Disorder><R & D><R&D><Radiation Oncology><Radiation therapy><Radiotherapeutics><Radiotherapy><Recurrence><Recurrent><Replication Error><Research><Research Design><Research Personnel><Research Resources><Researchers><Resources><Risk><Sampling><Scientist><Sequence Alteration><Solid><Somatic Mutation><Spirometry><Study Type><Teaching><Thorace><Thoracic><Thorax><Time><Tissues><Toxic effect><Toxicities><Training><Treatment outcome><Treatment-related toxicity><adverse consequence><adverse outcome><anti-cancer therapy><bio-markers><biobank><biologic marker><biomarker><biorepository><blood cell formation><cancer care><cancer prevention><cancer registry><cancer therapy><cancer-directed therapy><cardiac MRI><cardiac magnetic resonance imaging><cardiovascular disorder><care for patients><care of patients><career><career development><caring for patients><chemo-/radio-therapy><chemo-radio-therapy><chemo-radiotherapy><chemo/radiation therapy><chemoradiation><chemoradiation therapy><chemoradiation treatment><chemoradiotherapy><chemotherapy and radiotherapy><chromosomal defect><chromosome defect><clinical biomarkers><clinical candidate><clinically useful biomarkers><cohort><complex data><data registry><disease of the lung><disorder of the lung><electronic health care record><electronic health medical record><electronic health plan record><electronic health registry><electronic medical health record><entire genome><environmental mutagenesis><environmental mutagens><epidemiologic><epidemiological><exome sequencing><exome-seq><experience><full genome><genome mutation><genomic alteration><improved><insight><lung disorder><malignancy><mutation status><mutational status><neoplasm registry><neoplasm/cancer><novel><older groups><older individuals><older person><professor><programs><prospective><radiation or chemotherapy><radiation treatment><radio-chemo-therapy><radio-chemotherapy><radiochemotherapy><research and development><skill acquisition><skill development><skills><somatic variant><study design><therapeutic toxicity><therapy adverse effect><therapy associated toxicity><therapy related toxicity><therapy toxicity><treatment adverse effect><treatment toxicity><treatment with radiation><treatment-associated toxicity><whole genome>