Pamela Becker, M.D., Ph.D. Laboratory

The Becker lab focuses on novel therapy of acute myeloid leukemia (e.g.-RNA therapeutics) and drug resistance in blood cancers (e.g.-acute myeloid leukemia, myelodysplastic syndrome, multiple myeloma) based on clinical features, mutations, and gene expression, with use of high throughput functional screening/multicolor flow cytometry to directly assay drug response.

The iQue3 Sartorius instrument
Our lab utilizes the Sartorius iQue3, an advanced high-throughput flow cytometry system engineered for fast, automated, and highly multiplexed cellular analysis. The instrument features unique rapid-sampling technology, integrated automation, and user-friendly software that enable rapid data acquisition with minimal hands-on time. These capabilities support a wide range of applications, including immune profiling, phenotypic characterization, cell health assays, drug screening, and bead-based multiplexing. Its streamlined workflow allows us to efficiently process large numbers of samples while maintaining consistent, high-quality data.

Project 1

Title: Pilot Study for Individualized Treatment for Acute Myeloid Leukemia Based on High Throughput Screening and Genomics Data

This study will use high-throughput drug screening (HTS) to evaluate the sensitivity of patients’ leukemic cells to approximately 150 drugs and drug combinations, using bone marrow aspirate or peripheral blood blasts. Genomic and transcriptomic profiling through the HopeSeq targeted NGS and RNA-seq assays will further inform drug selection, while the CLIA-approved Cancer Drug Sensitivity Test (CDST) HTS provides faster functional results. Results from these assays will be integrated by a Functional Molecular Tumor Board to generate personalized treatment recommendations for patients with relapsed or refractory AML within 14–18 days of sample acquisition. Standard supportive therapies such as hydroxyurea or single-dose cytarabine will be permitted as needed to control blast counts prior to treatment.

Project 2:

Title: High-Throughput Functional Drug Screening to Identify Therapeutic Vulnerabilities in MDS Progression to sAML

Patients with high- or very high-risk MDS have poor survival due to progression to secondary AML and limited effective treatment options after relapse or transformation. To address this, we developed a multicolor flow cytometry–based high-throughput drug screening (MFC-HTS) platform to evaluate drug sensitivity in MDS and sAML patient samples. Using longitudinal genomic data and public multiomic datasets, we analyzed disease progression and tested a 64-drug panel on primary MDS and sAML samples, directly measuring CD34+ blast viability within a simulated marrow microenvironment. Drug response metrics and statistical analyses were used to identify promising agents and distinguish sensitivity patterns between MDS and sAML.

Project 3

Preclinical Studies of CXCR4 and β2-Adrenergic Receptor Expression in Acute Myeloid Leukemia

The objective of this project is to conduct translational preclinical studies evaluating CXCR4 inhibition in combination with β-adrenergic receptor blockade for the treatment of acute myeloid leukemia (AML). Prior studies have demonstrated that AML blasts depend on CXCR4 signaling for homing to and retention within the bone marrow niche, where the microenvironment confers protection from chemotherapy. Disruption of AML–bone marrow interactions has therefore emerged as an important therapeutic strategy.

This mechanism has previously been explored using CXCR4 inhibition with plerixafor (Sanofi), GPC-100/TG-0054 (GPCR Therapeutics, Inc.), small-molecule CXCR4 antagonists, and a CXCR4-targeting antibody (Bristol Myers Squibb), in combination with induction chemotherapy in both newly diagnosed and relapsed/refractory AML. The specific aims of this preclinical study are to 1. identify AML patient populations most likely to benefit from CXCR4 inhibition; 2. investigate the role of combined CXCR4 and β2-adrenergic receptor blockade; 3. determine whether combined CXCR4 inhibition with the novel agent GPC-100 (burixafor) and β2-adrenergic receptor blockade enhances cytarabine sensitivity of AML blasts in a stromal co-culture model.

Project 4

Transfection of RUNX1 mRNA–LNP in Patient-Derived Acute Myeloid Leukemia blasts

RUNX1 is a key transcription factor required for normal myeloid differentiation and is among the most frequently mutated transcription factors in AML. Both constitutional and acquired RUNX1 mutations contribute to leukemogenesis in a subset of AML patients; however, there are currently no targeted therapies available for these mutations. The objective of this study is to evaluate whether transfection of RUNX1 mRNA formulated in lipid nanoparticles (mRNA–LNP) can restore protein expression in patient-derived primary AML blasts harboring RUNX1 mutations. We will assess whether mRNA–LNP–mediated restoration of transcription factor expression modulates abnormal proliferation, promotes myeloid differentiation, and enhances sensitivity to standard chemotherapy and targeted agents.