Our Research

Discovering hidden cancer drivers to build better, less toxic therapies

By combining cancer genomics with drug development, we identify new therapeutic targets and design precision treatments — including small molecules, degraders, and antibody-drug conjugates — aimed at improving survival while reducing the harmful side effects of traditional therapies.

Themes in Our Work

  • Use of bioinformatics to identify kinases with mutations or alterations that drive or suppress cancer

  • Identification & validation of novel cancer drivers for cancers of unmet need

  • Development of the next generation of cancer therapies to target these cancer drivers

Check out our featured projects!

 

Defining LZK as a critical driver of head and neck and esophageal cancers.

Elucidate the mechanisms by which this kinase drives cancer cell viability and promote immune evasion, and develop novel treatment approaches to target this kinase including small molecule inhibitors, ADCs, and degraders.

  1. Edwards ZC, Trotter EW, Torres-Ayuso P, Chapman P, Wood HM, Nyswaner K, Brognard J. Survival of Head and Neck Cancer Cells Relies upon LZK Kinase-Mediated Stabilization of Mutant p53. Cancer Res. 2017 Sep 15;77(18):4961-4972. PMID: 28760853.

  2. Funk AL, Katerji M, Afifi M, Nyswaner K, Woodroofe CC, Edwards ZC, Lindberg E, Bergman KL, Gough NR, Rubin MR, Karpińska K, Trotter EW, Dash S, Ries AL, James A, Robinson CM, Difilippantonio S, Karim BO, Chang TC, Chen L, Xu X, Doroshow JH, Ahel I, Marusiak AA, Swenson RE, Cappell SD, Brognard J. Targeting c-MYC and gain-of-function p53 through inhibition or degradation of the kinase LZK suppresses the growth of HNSCC tumors. Sci Signal. 2025 Feb 11;18(873):eado2857. PMID: 39933019

  3. Katerji M, Bergman KL, Lindberg E, Rubin MR, Afifi M, Funk AL, Woodroofe CC, Nyswaner K, Karpińska K, Serwa R, Cappell SD, Marusiak A, Swenson RE, Brognard JF. Discovery of potent and selective PROTACs for the protein kinase LZK for the treatment of head and neck cancer. J Biol Chem. 2025 May;301(5):108452. PMID: 40157536.

 
 

Development of a new class of precision drug-antibody conjugates for cancers of unmet need

Ushering in a new era of ADC discovery, our PAC platform leverages small molecule inhibitors as payloads to target multiple oncogenic drivers within the same cancer cell. Designed to overcome resistance and pathway redundancy, PACs combine precise tumor targeting with coordinated inhibition of key signaling pathways—unlocking improved efficacy with reduced systemic toxicity.

 
 

Development of novel PROTACs to target kinases that promote tumorigenesis independent of catalytic activity

  • Ongoing research focused on:

  1. Developing a promising PROTAC to target TNK2 as a novel therapeutic target in ovarian cancer and LSCC

  2. Designing a degrader targeting PKCι for the treatment of lung cancer in collaboration with Dr. Allan Field at the Mayo clinic

  3. Generating a PROTAC targeting SLK in biliary tract and ovarian cancers in collaboration with Dr. Jonathan Hernandez lab at NIH

  4. Developing a degrader targeting PARP7 for treatment of numerous cancers with PARP7 amplifications (HNSCC, LSCC, ESCC) in collaboration with Dr. Ivan Ahel at Oxford University

  • Published work on PIM1 PROTAC to prevent the emergence of chemoresistance in prostate cancer

Read Article
 

Special thanks to our project funders