OHSU Knight Cancer Institute

Agarwal Lab

Anupriya Agarwal lab

Our laboratory is interested in understanding the interplay between genetic drivers and the factors in the tumor microenvironment so that disease can be identified at early stage and new therapeutic approaches can be uncovered for the treatment of leukemia patients. 

Projects

1. Genetic modalities and therapeutic targets in leukemia predisposition syndromes and clonal hematopoiesis models

Clonal evolution in Acute Myeloid Leukemia (AML) is the stepwise acquisition of secondary mutations starting from the preleukemic stage. Preleukemia is defined by germline mutations in leukemia predisposition syndromes and acquired mutations in clonal hematopoiesis. Understanding the mechanisms of disease transformation from the preleukemic stage is critical to identifying high-risk individuals and for developing early interventions. Our group is implementing cutting-edge methods and multi-parametric single cell analysis to perform comprehensive characterization of preluekemic primary samples and to identify new mechanisms of disease initiation. In addition, we perform functional dissection of identified pathways using in vivo mouse models and identify novel targeted therapies for early interventions.

Inter-and intra-institutional collaborations to identify markers of early detection

2. Extrinsic mechanisms that regulate hematopoiesis of healthy and malignant stem cells

We believe that the complex signaling milieu of the bone marrow microenvironment creates a selective pressure at early leukemic stage to promote clonal growth of leukemia cells. Consistent with this, we and others have identified several proinflammatory cytokines that have a paradoxical effect on clonal growth of leukemia cells while suppressing the growth of healthy nonmalignant cells. We are performing omics-based analyses to identify the molecular signature that leads to microenvironment-driven functional differences in nonmalignant and malignant stem cells. This comprehensive approach will allow us to gain insight into the signaling mechanisms that contribute to clonal growth of leukemic stem cells, enabling design of therapeutic strategies to target malignant cells specifically.

3. Mechanisms of molecular conduit between the microenvironment and leukemic cells in conferring drug resistance

It is likely that not only the bone marrow microenvironment but also leukemia cells reprogram their niche. For instance, treatment with cytotoxic therapy promotes the release of signaling mediators from leukemic cells that recruit immune cell responses from the microenvironment to blunt malignant cell killing.  Additionally, cytotoxic therapy-mediated reprogramming of the microenvironment may itself promote the survival of leukemic cells by releasing growth-promoting cytokines. We propose that delineating these mechanisms will establish a novel paradigm for designing therapeutic strategies to target aberrant microenvironment-driven signaling in leukemia.

3.	Mechanisms of molecular conduit between the microenvironment and leukemic cells in conferring drug resistance

Learn more

Since 2014, the Agarwal lab is generously funded by:

  • NIH/NCI K99/R00 Pathways to Independence Award
  • NIH/NCI R01 
  • V Foundation Scholar Award
  • American Cancer Society Research Scholar Grant
  • The Babich Family Foundation /Alex's Lemonade Stand Foundation
  • Pilot funds from the OHSU Knight Cancer Institute - Hillcrest Committee, CEDAR Research Project grant, and NIH Build Exito Pilot Project Award as well as collaborative projects through NCI U54 Drug Resistance and Sensitivity Network (DRSN) and U01 Clinical Proteomic Tumor Analysis Consortium  (CPTAC)
Funding for the Agarwal lab is provided by
Anupriya Agarwal, Ph.D.

Anupriya Agarwal, Ph.D.
Hematology & Medical Oncology
Molecular & Medical Genetics
Knight Cancer Institute

Education:
M.S., Microbiology, G.B. Pant Univ., India
Ph.D., Microbiology, Dr. R.M.L. Avadh Univ. and ITRC institute, India

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Adam Duvall

Adam Duvall, M.D.
Clinical Fellow

Education:
B.S., University of Notre Dame

M.D., Case Western Reserve University School of Medicine
M.P.H., Case Western Reserve University Department of Epidemiology and Biostatistics

Scientific interests: Adam’s clinical interest is to care and improve the outcomes of adolescents and young adults with cancer. His translational research examines the impact of inflammation on the development of acute leukemia in patients with germline mutations associated with leukemia predisposition syndromes (specifically RUNX1 mutations).

Hobbies: When not at work, Adam enjoys spending time outdoors in beautiful Portland with his wife, two children, and dog.

Rucha Modak, Ph.D.

Rucha Modak, Ph.D.
Postdoctoral Fellow

Education:
M.S., Tata Institute of Fundamental Research, India
Ph.D., Immunology and Infection, University of Edinburgh

Scientific interests: Rucha’s main interest is the interactions between AML cells and bone marrow microenvironment in the context of drug resistance.

Hobbies: Rucha enjoys traveling, hiking and listening to Indian classical music.

Hsin-Yun Lin, M.S.

Hsin-Yun Lin, M.S.
Graduate Student

Education:
B.S., Biotechnology, East China University of Science and Technology

M.S., Biological Engineering, University of Missouri

Scientific interests: Hsin-Yun is interested in understanding the molecular mechanisms of disease progression mediated by inflammatory cytokines in Acute Myeloid Leukemia progression.

Hobbies: She enjoys running with friends, reading short stories and baking coconut macaroons in her free time.

Mona M.Hosseini, B.S.
Graduate Student

Education:
B.S., Biology, minor, Chemistry, Portland State University

Scientific interests: Mona is interested in dissecting new signaling pathways involved in leukemia initiation and progression in the context of microenvironment in Acute Myeloid Leukemia.

Hobbies: Mona likes to hike and take pictures in her free time.

John McClatchy, B.S.

John McClatchy, B.S.
Graduate Student

Education
B.S., Biology and Bioveterinary Science, minors, Chemistry and Computer Science, Utah State University

Scientific interests: John is interested in developing strategies to identify and prevent  leukemia progression at early stage in familial Acute Myeloid Leukemia. He is approaching his research interest by characterizing the function of novel germline mutations and understanding their interactions with the inflammatory microenvironment.

Hobbies: John enjoys ballroom dance, longboarding, gymnastics, reading, skill-based games and free food.

Andrea Monteblanco, B.S.

Andrea Monteblanco, B.S.
Research Assistant

Education
B.S., Biology, Linfield College, Portland

Scientific interests: Andrea is interested in how genetic abnormalities drive cancer pathogenesis in Acute Myeloid Leukemia.

Hobbies: Andrea enjoys dancing and spending time with her friends and family.

Karina Thiel-Klare, B.S.

Karina Thiel-Klare, B.S.
Research Assistant

Education:
B.S., Marine Biology, minor, Organic Chemistry, University of Oregon

Scientific interests: Karina is interested in distinguishing factors that drive differences in malignant and nonmalignant cell growth and survival.

Hobbies: Karina enjoys hiking and reading.

Ruthey Viver

Ruthey Viver
Student Research Intern

Education: B.S. (in progress), Portland State University

Scientific interests: Ruthey is interested in understanding the role of genetic drivers in leukemia progression

Hobbies:  In her spare time Ruthey likes to serve, assist, and impact people of all ages through outreach programs.

Alisha Steigerwald

Alisha Steigerwald
Student Research Intern 

Education: B.S. (in progress), Portland State University

Scientific interests: Alisha’s research interests are the epigenetic mechanisms that contribute to the development of cancers and research investigating targeted immunotherapies for such cancers.

Hobbies: Alisha enjoys traveling, reading, and drawing

  • Alyssa Carey, Research Assistant
  • Megan Cleary, Sr. Research Assistant
  • Swati Garg, Graduate Student, Summer Rotation
  • Kristina Halvorson, Research Assistant
  • Clayton Hudson, Graduate Student, Rotation
  • Bernadette Maertens, Murdock Scholar
  • Alka Puri, Visiting Intern
  • Rhese Thompson, Murdock Scholar
  • Michie Degnin, Senior Research Assistant
  • Chris Eden, Research Assistant
  • Sherif Abdelhamed, Assistant Staff Scientist
  • Gabby Dewson, Murdock Scholar
  • Homma Khosroyani, Graduate Student, Rotation
  • Gabriel Cohn, Graduate Student, Rotation
  • Tiffany Lee, Medical Student Research Intern

Join our team

We are looking for enthusiastic and motivated individuals to join our lab. If you have a strong background in cell biology and the ability to perform basic computational analysis using large data sets, we'd love to hear from you.