HOME / BIO /

Who is Clarence?

Clarence is the Director of Microscopy and Image Analysis at the Laboratory of Systems Pharmacology (LSP) under Professor Peter Sorger, as well as a research associate at the Image and Data Analysis Core (IDAC) under Dr. Hunter Elliott, and regularly works with the Nikon Imaging Center (NIC) under Dr. Jennifer Waters at Harvard Medical School (HMS). His main interests are in aiding experimental design of imaging assays through collaboration, as well as applying deep learning to 2D, 3D and 4D image analysis problems.

  • actin and osteoclast

    Osteoclasts...

    ...are the cells that clear away bone and have a characteristic actin ring and multiple nuclei (sometimes as many as 30!)

  • Still good...

    A cell optoporated with propidium iodide (a DNA intercalator, shown in red) still managers to divide

  • BRD4

    It's a pile of FRAP!

    Fluorescence Recovery After Photobleaching (FRAP) can reveal how well a protein is bound to its target in presence of a drug

  • collagen

    Comparing extracellular matrix in disease and healthy tissue

    Collagen and elastin produce a unique second harmonic signal and two photon excitation fluorescence respectively

  • cell 7

    Dead or alive

    A temporary hole can be made in the cell membrane to allow proteins that normally would not enter a living cell

Highlighted Publications

Z Inde, C Yapp et al., 2020, Age-dependent regulation of SARS-CoV-2 cell entry genes and cell death programs correlates with COVID-19 disease severity, Biorxiv, doi: https://doi.org/10.1101/2020.09.13.276923

A Farkkila....C Yapp  et al., 2020, Immunogenomic profiling determines responses to combined PARP and PD-1 inhibition in ovarian cancer, Nat. Comm. 11, 1459

G Gaglia, R Rashid, C Yapp et al., 2020, HSF1 phase transition mediates stress adaptation and cell fate decisions, Nat. Cel. Biol., 22, 151-158

ML Onozato*, C Yapp*,(* contributed equally) et al., 2019, Highly Multiplexed Fluorescence in Situ Hybridization for in Situ Genomics, J Molecular Diagnostics, 21:3, 390–407

S Saka,...C Yapp, et al., ,2019, Highly multiplexed in situ protein imaging with signal amplification by Immuno-SABER, Nat. Biotech, 37(9), 1080

JR Lin, ...C Yapp, et al., 2018, Highly multiplexed immunofluorescence imaging of human tissues and tumors using t-CyCIF and conventional optical microscopes, Elife, 11,7: e31657

SB Hatch*, C Yapp*, (* contributed equally) et al., 2017, Assessing histone demethylase inhibitors in cells: lessons learned, Epigenetics and Chromatin, 10:9

C Yapp, U Oppermann, A Price et al., 2016, H3K27me3 demethylases regulate in vitro chondrogenesis and chondrocyte activity in osteoarthritis, Arthritis Res. Ther., 18(1):158

C Yapp, C Rogers, Pavel Savitsky et al., 2016, Frapid: achieving full automation of FRAP for chemical probe validation, Biomed. Opt. Express, 7(2):422-441

M Philpott, CM Rogers, C Yapp, et al., 2014, Assessing cellular efficacy of bromodomain inhibitors using fluorescence recovery after photobleaching, Epigenetics & Chromatin

RJ Hopkinson*, A Tumber*, C Yapp* (* contributed equally) et al., 2013, 5-Carboxy-8-hydroxyquinoline is a broad spectrum 2-oxoglutarate oxygenase inhibitor which causes iron translocation. Chemical Science

 

 

Research Interests

During his DPhil study, he developed optoporation, a near-infrared laser microscopy technique to introduce biological macromolecules into living cells. He spent four years as a postdoctoral scientist at the Structural Genomics Consortium and Target Discovery Institute (Oxford, UK), where his project took his fascination in applying optical methods for understanding and manipulating biology to develop image-based high-content phenotypical cell-based assays. To identify potent small molecule inhibitors against novel epigenetic targets, he designed a Fluorescence Recovery After Photobleaching (FRAP) assay and a histone mark immunofluorescence assay, which are now routinely used to validate chemical probes against bromodomains (ATAD2, BRD4, BRPF1B, BRD9, CECR2, CREBBP, and SMARCA) and demethylases (JARID1B, JMJD1, JMJD2A, JMJD3, and FBXL11) respectively. His assays have led to the declaration of over 20 chemical probes that are now freely distributed through the SGC and are being used to probe the biological functions of these new targets. In May 2013, Clarence wrote and was awarded a grant to further develop and automate the FRAP assay, which led to a 4-fold increase in data throughput. During his time as a postdoctoral scientist, he also served as the microscopy facility manager at the Botnar Research Centre and Target Discovery Institute where he provided collaborative experimental design on 16 wide ranging projects that utilized timelapse, single and multiphoton, and high content microscopy towards the fields of stem cell differentiation, inflammation, DNA damage, and 3D scaffolds for tissue engineering and regeneration.

At the LSP and IDAC, Clarence aims to apply his interests in new microscopy techniques and unsupervised machine learning image analysis algorithms to solve problems.