Daniel Alexander King, MD, PhD (Oncology Fellow)
Originally from Long Island, NY, Dan trained at Cold Spring Harbor Laboratory, the University of Michigan (BS), Wayne State University (MD), the National Human Genome Research Institute (HHMI Research Scholars Program), Cambridge University (PhD), and Columbia University (Internal Medicine Residency). He enjoys mutation hunting in large-scale genomic data. He was most recently involved in an exome sequencing study of 12,000 children with rare disease and their parents, in which he developed new computational tools to identify large genetic aberrations. His mutational spectrum of interest includes uniparental disomy, copy number alterations, and mosaicism. He plans to explore research opportunities riding the intersection of new technology & genomics, such as single cell DNA & RNA sequencing, and circulating tumor DNA.
During oncology fellowship he has developed a passion for pancreatic cancer and specializes in caring for patients with pancreatic cancer in clinic with renowned medical oncologist Dr George Fisher. During fellowship his pancreatic research interests span the spectrum of translational research in pancreatic cancer. Several recent accomplishments include: 1) the development of a pancreatic cancer-specific circulating tumor DNA assay, the development of a pancreatic cancer research database containing thousands of patients who presented to Stanford with pancreatic cancer over the last twenty years, and the development of a large +500 sample biobank consisting of blood samples from generous pancreatic cancer patient study participants.
- Association of Pharmacogenetics With Adverse Events of Fluorouracil/Capecitabine in Patients With Cancer. JCO oncology practice 2021: OP2001072
PERHAPS: Paired-End short Reads-based HAPlotyping from next-generation Sequencing data.
Briefings in bioinformatics
The identification of rare haplotypes may greatly expand our knowledge in the genetic architecture of both complex and monogenic traits. To this aim, we developed PERHAPS (Paired-End short Reads-based HAPlotyping from next-generation Sequencing data), a new and simple approach to directly call haplotypes from short-read, paired-end Next Generation Sequencing (NGS) data. To benchmark this method, we considered the APOE classic polymorphism (*1/*2/*3/*4), since it represents one of the best examples of functional polymorphism arising from the haplotype combination of two Single Nucleotide Polymorphisms (SNPs). We leveraged the big Whole Exome Sequencing (WES) and SNP-array data obtained from the multi-ethnic UK BioBank (UKBB, N=48,855). By applying PERHAPS, based on piecing together the paired-end reads according to their FASTQ-labels, we extracted the haplotype data, along with their frequencies and the individual diplotype. Concordance rates between WES directly called diplotypes and the ones generated through statistical pre-phasing and imputation of SNP-array data are extremely high (>99%), either when stratifying the sample by SNP-array genotyping batch or self-reported ethnic group. Hardy-Weinberg Equilibrium tests and the comparison of obtained haplotype frequencies with the ones available from the 1000 Genome Project further supported the reliability of PERHAPS. Notably, we were able to determine the existence of the rare APOE*1 haplotype in two unrelated African subjects from UKBB, supporting its presence at appreciable frequency (approximatively 0.5%) in the African Yoruba population. Despite acknowledging some technical shortcomings, PERHAPS represents a novel and simple approach that will partly overcome the limitations in direct haplotype calling from short read-based sequencing.
View details for DOI 10.1093/bib/bbaa320
View details for PubMedID 33285565
- Marked Decrease in CA 19-9 Level Belies Rapidly Progressive Lymphangitic Carcinomatosis in a Case of Metastatic Pancreatic Cancer JOURNAL OF PANCREATIC CANCER 2020; 6 (1): 102–6
- Chromatin accessibility patterns in cell-free DNA reveal tumor heterogeneity AMER ASSOC CANCER RESEARCH. 2020
Detection of circulating tumor DNA in pancreas cancer
AMER SOC CLINICAL ONCOLOGY. 2020
View details for Web of Science ID 000530922700623
Marked Decrease in CA 19-9 Level Belies Rapidly Progressive Lymphangitic Carcinomatosis in a Case of Metastatic Pancreatic Cancer.
Journal of pancreatic cancer
2020; 6 (1): 102–6
Background: The CA 19-9 tumor marker is commonly used alongside imaging to trend chemotherapy response in patients with pancreatic ductal adenocarcinoma. Presentation: We describe an unusual clinical case of metastatic pancreatic cancer who achieved a marked decline in CA 19-9 but paradoxically developed widespread pulmonary lymphangitic carcinomatosis leading to rapid clinical decline and death. Conclusions: This case highlights the limitations of using the CA 19-9 tumor marker in isolation.
View details for DOI 10.1089/pancan.2020.0015
View details for PubMedID 33269335
View details for PubMedCentralID PMC7703254
- Linked read whole genome sequencing reveals pervasive chromosomal level instability and novel rearrangements in brain metastases from colorectal cancer AMER ASSOC CANCER RESEARCH. 2018