Michael Green, PhD

Assistant Professor, Eppley Institute

Tel: 402-559-2088
Email: Michael Green

Michael Green, Ph.D.

Education

BBMedSc (1°Hons), Victoria University of Wellington, New Zealand.
PhD, School of Health Sciences, Griffith University, Queensland, Australia.
Postdoc, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
Postdoc, School of Medicine, Stanford University, Stanford, CA.

Research Interests

The focus of the Green laboratory is to unravel the genetic underpinnings of lymphoid malignancies, with the ultimate goal of identifying and therapeutically targeting the molecular drivers of these cancers.

Background

The majority of lymphoid malignancies originate from B-cells, the antibody producing cells of the body. These cells undergo a complex process of differentiation and interact on multiple levels with other immune cells. Despite the natural checkpoints in place that regulate B-cell development and survival, genetic alterations can allow malignant B-cells to accumulate at a range of differentiation states; from early B-cell progenitors (e.g. for B-cell acute lymphoblastic leukemia [B-ALL]), to germinal center B-cells (e.g. for diffuse large B-cell lymphoma [DLBCL], Burkitt’s Lymphoma [BL] and follicular lymphoma [FL]), to plasma cells (e.g. for Multiple Myeloma [MM]). Each of these diseases possess unique mechanisms for exploiting the advantages and avoiding the disadvantages associated with their specific differentiation state. In addition, the malignant cells exist in close association with other non-malignant immune cells and develop mechanisms for avoiding immune destruction. Perturbations in normal B-cell biology and immune interactions are therefore attractive therapeutic targets in these diseases and a core focus of our laboratory.

Our Approach

Discover the Target, Delineate the Mechanism, and Direct a Therapy.

To discover the target, we employ high-throughput genomic technologies such as next-generation sequencing (NGS) to interrogate the genomes and transcriptomes of primary human tumors. We use these genome-wide approaches to identify genes/mutations that are important for tumor biology because of their roles in disease genesis, their involvement in immune deregulation, or their association with patient characteristics such as therapeutic response or survival time.

In order to delineate the mechanism by which genes/mutations contribute to disease biology, we use genetic manipulation of lymphoma cell-lines. This includes reconstituting the expression of deleted/silenced genes with viral vectors, or using CRISPR technology to introduce mutations to the somatic genome. These manipulations provide paired cell-lines with or without specific alterations that can be compared for innate properties, such as proliferation or apoptosis, or for their capacity to interfere with the function of co-cultured healthy immune cells.

The objective of this research is to direct a therapy that inhibits or counteracts the molecular consequences of genetic alterations. This is achieved by; (i) knowledge-driven repurposing of approved therapeutics based upon their defined mechanisms of action, (ii) developing new immunotherapies to neutralize/agonize a perturbed immune axis, or (iii) using high-throughput synthetic lethality screens with small molecule libraries to identify lead compounds.

Selected Publications