NATIONAL CANCER INSTITUTE - CANCER.GOV

Contact Information

Primary Contact

Kerstin Heselmeyer-Haddad
Head, Wet Lab

Location

Building 37, Room 6138
Bethesda, MD 20892

Additional Contacts

Patrick Zhao
Head, Bioinformatics

Overview

Our operational objectives are to provide state-of-the-art OMICS technologies in support of the Genetics Branch (GB) investigators and collaborators.
Research Services

Wet Lab

  • Single cell isolation from fresh, frozen, and FFPE tissue
  • DNA/RNA extractions from fresh, frozen, FFPE tissue, and tissues preserved by other methods
  • Cell free circulating DNA from plasma and serum
  • Quality assessment of nucleic acids by spectrophotometry, fluorometry, qPCR, capillary electrophoresis, digital droplet PCR
  • Next-generation sequencing (NGS) library preps
  • Sequencing (Whole genome sequencing including low pass (WGS) and whole transcriptome sequencing (WTS), whole exome sequencing (WES), panel, low-pass WGS for copy number variations)
  • ChIP-Seq, Cut&Run
  • Meso scale discovery (MSD) protein detection
  • Fluorescence in situ hybridization (copy number evaluation for specific genes, fusion or break-apart probes)
  • miFISH (novel method to hybridize, scan and enumerate up to 35 multicolored FISH probes within the same nucleus, can evaluate hundreds to thousands of cells)
  • Spectral karyotyping (SKY - visualizing each chromosome in a specific color to decipher complex karyotypes)
  • Custom-Need Assay Development: Other potential applications would include single-cell RNA-Seq, CITE-Seq, single-cell DNA-Seq, and single-cell ATAC-Seq, as well as long-read WGS and WTS. There are plans to introduce new biological technologies, such as single-cell enhancer mapping combined with scRNA-Seq, and new proteomics-based assays.

Bioinformatics

  • Data Analytics. Currently, we offer integrated OMICS data analytics support and facilitate the interpretation of large-scale omics data from short- and long-read NGS, including WES and WGS, WTS, ChIP-Seq, Cut&Run and Cut&Tag, and single-cell technologies. The team is expanding its data analytics capabilities into three-dimensional (3D) genome profiling and spatial transcriptomics and proteomics.
  • Bioinformatics Research and Development. We conduct need-based bioinformatics research and development, such as implementing bioinformatics pipelines to meet new data analytics demands.
  • Omics Data Integration and Presentation. We develop and maintain cancer genomics databases for data integration and web-based visualization. These provide biologists, physicians, and trainees with easy access to omics data.
  • Big Data and Data Science. We facilitate the GB investigators’ increasing utilization of public datasets, and a future direction will include the development of deep/machine learning (including artificial neural networks (ANN) and convolutional neural networks (CNN)) to study human cancer data.
  • High-performance Computing in Bioinformatics. We enable GB researchers to effectively use high-performance computing clusters (HPCs, i.e., Biowulf), AWS cloud computing, and the Amazon Genomics Command Line Interface (CLI) tools in their analyses.
  • Data Management. We manage large-scale raw and processed next-generation sequencing (NGS) datasets using the NCI High Performance Computing Data Management Environment (HPC DME).
  • Data Submission to Public Databases. We provide assistance to PIs to upload data to public resources such as dbGaP, GEO, Imaging Data Commons, Genomic Data Commons, Proteomic Data Commons, and others.
  • Hands-on Bioinformatics Training and Consulting. We provide training for GB staff and trainees in performing their own analysis. The team also advises researchers on experimental design and recommends tools and methods for data processing and interpretation.

Major Instrumentation

                                      SQ120-MSD protein detection (Meso Scale Discovery)

                                      Digital droplet generator and Digital droplet reader (BioRad QX200 Droplet Digital PCR System)

                                      Bioview Automated Spotcounting microscope (FISH)

                                      Leica ThunderImager for FISH and Brightfield

                                      ASI Spectral Karyotyping microscope (SKY)

                                      Maxwell RSC instrument

                                      NextSeq 500 and NextSeq 2000 Illumina sequencers

                                      Agilent Bioanalyzer

                                      Covaris Sonicator

                                      User Guidelines

                                      Collaborators outside the Genetics Branch are welcome, but proposals should be collaborative with a GB PI to access the GB OMICS services.

                                      Publications

                                      • Schru00f6ck E, du Manoir S, Veldman T, Schoell B, Wienberg J, Ferguson-SmithMA, Ning Y, Ledbetter DH, Bar-Am I, Soenksen D, Garini Y, Ried T. Multicolor spectral karyotyping of human chromosomes. Science. 1996 Jul 26;273(5274):494-7.
                                      • Hilgenfeld E , Montagna C, Padilla-Nash H, Stapleton L, Heselmeyer-Haddad K, Ried T. Spectral karyotyping in cancer cytogenetics. Methods Mol Med. 2002;68:29-44.
                                      • Heselmeyer-Haddad K, Berroa Garcia LY, Bradley A, Ortiz-Melendez C, Lee WJ, Christensen R, Prindiville SA, Calzone KA, Soballe PW, Hu Y, Chowdhury SA, Schwartz R, Schu00e4ffer AA, Ried T. Single-cell genetic analysis of ductal carcinoma in situ and invasive breast cancer reveals enormous tumor heterogeneity yet conserved genomic imbalances and gain of MYC during progression. Am J Pathol. 2012 Nov;181(5):1807-22.
                                      • Oltmann J, Heselmeyer-Haddad K, Hernandez LS, Meyer R, Torres I, Hu Y, Doberstein N, Killian JK, Petersen D, Zhu YJ, Edelman DC, Meltzer PS, Schwartz R, Gertz EM, Schu00e4ffer AA, Auer G, Habermann JK, Ried T. Aneuploidy, TP53 mutation, and amplification of MYC correlate with increased intratumor heterogeneity and poor prognosis of breast cancer patients. Genes Chromosomes Cancer. 2018 Apr;57(4):165-175.
                                      • Strauss J, Heery CR, Schlom J, Madan RA, Cao L, Kang Z, Lamping E, Martu00e9 JL, Donahue RN, Grenga1 I, Cordes L, Christensen O, Mahnke L, Helwig C, Gulley JL. Phase 1 trial of M7824 (MSB0011359C), a bifunctional fusion protein targeting PD-L1 and TGF-u03b2, in advanced solid tumors. Clin Cancer Res. 24(6):1287-1295, 2018.
                                      • Yu Y, Ryan BM, Thomas A, Morrow B, Zhang J, Kang Z, Zingone A, Onda M, Hassan R, Pastan I, Cao L. Elevated serum megakaryocyte potentiating factor as a predictor of poor survival in patients with mesothelioma and newly diagnosed lung cancer. J Appl Med Lab. 3:166-177, 2018.
                                      • Cao L, Yu Y, Thomas A, Zhang J, Onda M, Meltzer P, Hassan R, Pastan I. Megakaryocyte potentiating factor as a predictive biomarker for therapies against malignant mesothelioma. J Clin Oncol Precision Oncology DOI: 10.1200/PO.17.00282, 2018.
                                      • Brown D, Zingone A, Yu Y, Zhu B, Candia J, Cao L, Ryan BM. Relationship between circulating inflammation proteins and lung cancer diagnosis in the National Lung Screening Trial. Cancer Epidemiol Biomarkers Prev. doi: 10.1158/1055-9965, 2019.
                                      • Meaney CL, Mitchell KA, Zingone A, Brown D, Bowman E, Yu Y, Wenzlaff AS, Neslund-Dudas C, Pine SR, Cao L, Schwartz AG, Ryan BM. Circulating Inflammation Proteins Associated with Lung Cancer in African Americans. J Thorac Oncol. 14:1192-1203, 2019.
                                      • Zimmer AS, Nichols E, Cimino-Mathews A, Peer C, Cao L, Lee MJ, Kohn EC, Annunziata CM. A phase I study of the PD-L1 inhibitor, durvalumab, in combination with a PARP inhibitor, olaparib, and a VEGFR1-3 inhibitor, cediranib, in recurrent womenu2019s cancers with biomarker analyses. J Immunother Cancer. 25;7:197. doi: 10.1186/s40425-019-0680-3, 2019.
                                      • Goklemez S, Im AP, Cao L, Pirsl F, Steinberg SM, Curtis LM, Mitchell SA, Cowen EW, Baruffaldi J, Rose J, Mays J, Ostojic A, Holtzman NG, Hakim FT, Pavletic SZ. Clinical characteristics and cytokine biomarkers in patients with chronic graft-vs-host disease persisting seven or more years after diagnosis. Am J Hematol. doi: 10.1002/ajh.25717, 2020.
                                      • JM Lee, CM Annunziata, JL Hays, L Cao, P Choyke, M Yu, D An, IB Turkbey, LM Minasian, SM Steinberg, H Chen, J Wright, EC Kohn. Phase II trial of bevacizumab and sorafenib in recurrent ovarian cancer patients with or without prior-bevacizumab treatment. Gynecol Oncol. 159:88-94. 2020.
                                      • Apolo AB, Nadal R, Tomita Y, Davarpanah NN, Cordes LM, Steinberg SM, Cao L, Parnes HL, Costello R, Merino MJ, Folio LR, Lindenberg L, Raffeld M, Lin J, Lee MJ, Lee S, Alarcon SV, Yuno A, Dawson NA, Allette K, Roy A, De Silva D, Lee MM, Sissung TM, Figg WD, Agarwal PK, Wright JJ, Ning YM, Gulley JL, Dahut WL, Bottaro DP, Trepel JB. Cabozantinib and peripheral immunity in advanced urothelial carcinoma: Final results from an open-label, phase II trial. Lancet Oncol. 2020 Jul 6:S1470-2045(20)30202-3. doi: 10.1016/S1470-2045(20)30202-3.
                                      • Curtis LM, Ostojic A, Venzon DJ, Holtzman NG, Pirsl F, Kuzmina ZJ, Baird K, Rose JJ, Cowen EW, Mays JW, Mitchell SA, Parsons-Wandell L, Joe GO, Comis LE, Berger A, Pusic I, Peer CJ, Figg WD, Cao L, Gale RP, Hakim FT, Pavletic SZ. A randomized phase 2 trial of pomalidomide in subjects failing prior therapy for chronic graft-versus-host disease. Blood. 137:896-907. 2021.
                                      • Goklemez S, Saligan LN, Pirsl F, Holtzman NG, Ostojic A, Steinberg SM, Hakim FT, Rose JJ, Kang Z, Yu Y, Cao L, Mitchell SA, Im A, Pavletic SZ. Clinical characterization and cytokine profile of fatigue in hematologic malignancy patients with chronic graft-versus-host disease. Bone Marrow Transplant. doi: 10.1038/s41409-021-01419-2. 2021.
                                      • Canter JA, Ernst SE, Peters KM, Carlson BA, Thielman NRJ, Grysczyk L, Udofe P, Yu Y, Cao L, Davis CD, Gladyshev VN, Hatfield DL, Tsuji PA. Selenium and the 15kDa Selenoprotein Impact Colorectal Tumorigenesis by Modulating Intestinal Barrier Integrity. Int J Mol Sci. 22:10651. doi: 10.3390/ijms221910651. 2021.
                                      • Girardi DM, Niglio SA, Mortazavi A, Nadal R, Lara P, Pal SK, Saraiya B, Cordes L, Ley L, Sierra Ortiz O, Cadena J, Diaz C, Bagheri H, Redd B, Steinberg SM, Costello R, Chan KS, Lee MJ, Lee S, Yu Y, Gurram S, Chalfin HJ, Valera V, Figg WD, Merino M, Toubaji A, Streicher H, Wright JJ, Sharon E, Parnes HL, Ning YM, Bottaro DP, Cao L, Trepel JB, Apolo AB. Cabozantinib Plus Nivolumab Phase I Expansion Study in Metastatic Urothelial Carcinoma Patients Refractory to Immune Checkpoint Inhibitor Therapy. Clin Cancer Res. doi: 10.1158/1078-0432. 2022,
                                      • Yu Y, Esposito D, Kang Z, Lu J, Remaley AT, De Giorgi V, N Chen LN, West K, Cao L. mRNA vaccine-induced antibodies more effective than natural immunity in neutralizing SARS-CoV-2 and its high affinity variants. Sci Rep, 12:2628. doi: 10.1038/s41598-022-06629-2. 2022.
                                      • Zhang X, Yu Y, Peer CJ, Landsman R, Skorupan N, Cao L, Alewine C. Low serum mesothelin in pancreatic cancer patients results from retention of shed mesothelin in the tumor microenvironment. Transl Oncol, doi: 10.1016/j.tranon.2022.101440. 2022.

                                      Keywords

                                      AWS cloud computingAmazon Genomics Command Line Interface (CLI)Bioinformatics pipelineBioview automated scannerBiowulfCancer genomicsChIP-SeqCut&RunDNA/RNA extractionsEpigeneticsExome and genomeFISHLeica ThunderImagerLibrary prepMSD protein detectionNGS data analyticsOMICS data analyticsOMICS technologiesSKYSequencing (WES WGS low-pass WGS for copy number variations RNA-seq)Single-cell technologiesSpatial transcriptomicsWhole transcriptomeddPCRmiFISHqPCR