Doernbecher Children's Hospital

Davare Lab

Overview

Our broad research objectives are to discover cell intrinsic pathways that promote oncogenesis and malignant progression of tumors, with a special interest in rare but aggressive pediatric and adult cancers including  sarcoma, low and high grade glioma and lung cancer. Concomitantly we identify and test effective, targeted pharmacological agents that are amenable for clinical implementation as cancer treatments. Associated efforts to pre-emptively identify mechanisms of clinical resistance and discovery of second-line therapies have permitted us to successfully bridge bench research to clinical trials. We are also attempting to innovate approaches to target tumor immune-evasion mechanisms to enable combination therapies in genomically complex cancers that do not respond to monotherapy with kinase inhibitors. In the midst of this translational research, we hope to unravel novel molecular insights into mechanisms of cellular signaling in both normal and cancer cells, particularly for those genes whose function is yet poorly characterized.

We have an overarching interest in elucidating the biological role and biochemical regulation of kinase aberrations in cancer cells. In the last few years, our focus has been on identifying novel oncogenic aberrations in and best therapeutic model to target ROS1, NTRK and ALK in pediatric and adult cancers. Ongoing work includes HTS pharmacological approaches, elucidating resistance pathways and structure function studies for these kinases, with strong focus on ROS1. Notably, as far as its role in normal cells goes, ROS1 remains somewhat of an enigma; it has the largest extracellular domain of human RTKs and the ligand as well as its physiological role in normal cells remains unknown. Some ongoing projects in the laboratory include:

  • Functional impact of somatic ROS1 aberrations discovered in cancer patients
  • Pre-emptive prediction of resistance to targeted therapy in ROS1 driven cancers
  • Role of ROS1 in glioblastoma
  • Physiological regulation of and by ROS1 in normal human cells

Our laboratory research group is also interested in validated effective therapeutic modalities for aggressive cancers driven by kinase gene fusions, or treatment-refractory histology, such as sarcomas.

  • Effectively targeting ROS1, NTRK, and ALK  fusion proteins in cancer
  • Discovery of novel compounds to target Ewing’s sarcoma
  • Efficacy of targeted therapeutics in spindle cell rhabdomysarcoma
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Zoe Beach
M.D./Ph.D. Candidate – Grad2

Originally from Redlands, California, Zoe completed a B.A. in Biochemistry at Oberlin College in 2017. During her time at Oberlin, Zoe completed her honors research thesis investigating the use of DNA aptamers for ovarian cancer biomarkers under the mentorship of Dr. Rebecca Whelan.  After graduating, Zoe moved to Portland and worked as a research assistant with Dr. Melissa Wong and Dr. Jerry Jaboin prior to matriculating into the MD/PhD program at OHSU in 2019. During her time at OHSU, Zoe has developed a passion for neurosurgery and is investigating molecular mechanisms behind tumor derived epilepsy with her clinical mentor, Dr. Ahmed Raslan. Currently, Zoe is pursuing her PhD in our laboratory where she is interrogating the role of oncogenic RTKs in adult and pediatric brain tumors. Outside of science, her other passion is aerial circus arts. Zoe has trained and performed as an aerial trapeze artist for 15 years and still trains every chance she gets.

A photo of Kristen Jones wearing a Nerf vest talking.

Kristen Jones, B.A.
Research Associate

Kristen received her B.A in Biology from Concordia University Portland. She spent two years working on Calcium Calmodulin Kinases in Drosophilia Melanogaster in Dr. Tom Soderling’s lab. From there she joined Dr. Sarah Smolik looking at CBP/P300 and its regulation of the cell cycle in flies, as well as honing her Photoshop skills. Finally settling in to Dr. Mike Forte’s lab until his retirement in 2019. She worked extensively with CRISPR/Cas9 to make changes to OSCP and CypD, part of the mitochondrial permeability transition pore. She now serves as Lab Manager in the Davare Lab. In her spare time, she enjoys travel, soccer, domesticated animals, Netflix binges, bike rides, reading, and Nerf wars.

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Charles de Leeuw, M.D., M.S., Ph.D.
PGY-3 Neurosurgery Resident

Research Interests: Functional genomics for identifying novel cancer therapies and combination chemotherapy. Other Interests: Sci-fi and horror movies, traveling, working out at the gym, playing tennis, and skiing.

A photo of Clare Keddy sitting at an outdoor table of a restaurant with two plates of food in front of her.

Clare Keddy, B.A.
Senior Research Assistant

Originally from Northern California, Clare moved to Portland to attend Lewis and Clark College. During her senior year, she worked in the Davare lab as part of the Murdock Research Internship Program. Clare now joins the Davare Lab full time after graduating in 2019. She is currently working on resistance mutations in ROS1. She enjoys rugby, dogs, and celery.

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Katelyn Nicholson, B.A.
Research Assistant II

Katelyn received her BA in Biochemistry and Molecular Biology from Lewis and Clark College in Portland, OR in May 2021. In her undergrad, she worked in the Hermann lab studying lysosome related organelles with C. elegans. In the Davare lab, she is researching the mechanism of action of a compound that targets Ewings Sarcoma. Outside of lab, Katelyn can be found listening to true crime podcasts, reading, and exploring different neighborhoods in Portland.

A selfie of Kevin Nusser making a funny face.

Kevin Nusser, Ph.D.
Research Associate

Kevin Nusser is a native eastern Oregonian and got his BS at Oregon State in microbiology before getting degrees at UHawaii (MS in animal science), Penn State (Ph.D. in physiology) and PacificU (MA in education). He started his science career in the lab of David Barnes at OSU studying proto-oncogenes in 1985. He did a post-doc in Charleston, South Carolina studying maternal factors in milk on neonatal development before moving back to Oregon in 1996 after his only kid, Sarah, was born. Since then he has been jumping around labs at OHSU working with Malcolm Low in the Vollum, Don Wolf and Shoukhrat Mitalipov at ONPRC, Peter Gillespie-Barr in the OHRC, Kathy Grant at ONPRC, Lara Davis in the KCI and now with Dr. Davare in Hem Onc. When not in lab, Kevin does improv with his independent group Urban Leopard, stand-up comedy and attends a local American Haiku meeting. He reads too much and writes too much and on his days off you will find him at the bins hoarding books, or volunteering as a human/guinea pig chimera. His favorite science quote is from Hippocrates, “Science and opinion are two different things; science is the father of knowledge but opinion breeds ignorance”.  For his last birthday, he flew to London to see the original Watson and Crick DNA model.

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Rajat Thawani, M.D.
Hematology/Oncology Fellow

Rajat is currently a hematology-oncology fellow at the Knight Cancer Institute at OHSU! He went to medical school at University of Delhi, India, and completed his internal medicine residency at Maimonides Medical Center in Brooklyn. He wants to be an early phase oncologist with interest in thoracic and head and neck malignancies. He splits his time between seeing patients at the VA and Phase I clinic at OHSU, and the Davare Lab where he is currently working on lung cancer, specifically understanding novel ways to target mutated non-small cel lung cancers. Outside of work, he likes to fly to NYC every chance he gets, try different restaurants, cook, hike and bike!

A professional photo of Yianyue Yang.

Qianyue Yang, B.E.
Research Assistant II

Ms. Yang is a Research Assistant in the Papé Pediatric Research Institute where she supports multiple laboratories with equipment repairs, maintenance, training of staff, and experimenting with cell cultures. Previously, Qianyue was a Senior Electric Engineer in China specializing in automatic systems control and quality control.

A collage of photos of the pets that belong to the Davare Lab members.
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Raveena Bhui
(Class of 2021, University of Washington)
OHSU Cell, Developmental and Cancer Biology Summer Internship Program

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Theo Truong
(Currently - Medical Student, OHSU)
Murdock Research Internship Program (2017)

Kelsey Yutan (Scripps College)

Madeline Eller (Wheaton College)

Sudarshan Iyer, B.S.E.
M.D./Ph.D. Student
iyesu@ohsu.edu
Graduated with Ph.D. in 2022. Currently back in M.D./Ph.D. Clinical Rotations.

Florence Choo, M.D.
Pediatric Hematology/Oncology Fellow
Currently Board Certified Pediatric Oncologist

Jacob Henderson, M.D.
Pediatric Hematology/Oncology Fellow
Currently Board Certified Pediatric Oncologist

Chelsea Jenkins, Ph.D.
Postdoctoral Fellow
Currently Senior Research Associate in Knight Cancer Institute (OHSU)

Nicolle Hofmann, Ph.D.
Senior Research Assistant
Currently Clinical Research Coordinator – OHSU Knight Cardiovascular Institute

Erin Aguero
Research Assistant II
Curently Graduate Studies in Genetic Counseling
University of Minnesota

Anna Pickering, Ph.D.
Postdoctoral Fellow
Currently Freelance Medical Writer

Contact

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