Susanta Hui Lab

To transform therapy, one must first see disease in its full physiological and spatial context. The Hui Lab is pioneering multimodal imaging platforms that visualize and quantify bone marrow activity, enabling a 3-D understanding of marrow function and disease dynamics.

Using PET-MRI, water-fat MRI (wfMRI) and dual-energy CT (DECT), Dr. Hui’s team has created the first spatial atlas of the human skeleton — a “Google Earth” of the marrow microenvironment. This innovation maps marrow adiposity, cellularity and proliferation in real time, enabling:

• Quantitative visualization of marrow regeneration and treatment response
• Noninvasive detection of disease relapse
• Site-specific functional total marrow irradiation (fTMI) to deliver precision radiation while sparing healthy tissue

Together, this imaging framework is redefining biological understanding of skeletal physiology and advancing the precision design of radiation therapy, bridging molecular insight with therapeutic application.

The Hui Lab investigates how bone marrow structure, aging and immune dynamics influence disease progression and post-therapy recovery. These studies integrate single-cell multi-omics, spatial imaging and in vivo models to elucidate the cellular and molecular orchestration of marrow regeneration.

Leukemia Relapse and the Bone Marrow Micro-Environment

Genetic mutations alone do not fully explain leukemia relapse following transplantation. By combining imaging with single-cell transcriptomics and spatial mapping, Dr. Hui’s team is uncovering how the bone marrow microenvironment facilitates immune escape and residual disease survival. These insights are yielding spatial biomarkers capable of predicting relapse and informing real-time therapeutic intervention.

Radiation, Gut Injury and Graft-Versus-Host Disease

Acute graft-versus-host disease (aGVHD) frequently targets the gastrointestinal tract. The Hui Lab uses spatially resolved imaging and multi-omic profiling to map how focal epithelial injury, microbiome disruption and immune infiltration interact to drive GVHD. This work aims to identify regenerative strategies and precision radiation approaches that protect the gut while preserving graft-versus-leukemia (GVL) effects.

Aging and Marrow Regeneration

Older adults undergoing transplantation experience higher relapse and toxicity rates due to senescent, inflamed marrow niches. The Hui Lab demonstrated that aged mice tolerate high-dose TMI and support effective engraftment — findings now translated into clinical practice. In a clinical trial (NCT03494569) involving patients 60 years old and over, total marrow and lymphoid irradiation (TMLI) achieved promising two-year relapse and non-relapse mortality rates (20% and 15%, respectively). Current studies integrate PET-MRI, single-cell analysis and senescence profiling to define how aging alters marrow recovery. Parallel preclinical models test senolytics and mesenchymal stromal cell (MSC) co-infusion strategies to rejuvenate marrow.

Dr. Hui’s lab translates biological discovery into clinical application, designing radiation and immunotherapy platforms that not only eradicate disease but also restore physiological balance.

Next-Generation TMI/TMLI and Adoptive Immunotherapy

The lab’s dual-function TMI/TMLI platform enhances immune modulation within the bone marrow while minimizing gastrointestinal toxicity. When combined with adoptive regulatory and conventional T-cell (Treg/Tcon) therapies, these approaches promote GVL benefits while reducing graft-versus-host disease (GVHD). Ongoing preclinical and clinical investigations (NCT04284587) are evaluating this integrative strategy.

In parallel, the lab is developing adjuvant immunomodulators, including STAT3-TLR9 inhibitors (CSI), to further enhance GVL while preserving tissue integrity.

Complementing these advances, Dr. Hui’s group has developed anti-CD33 PET tracers ([⁶⁴Cu]Cu-DOTA-anti-CD33) to noninvasively visualize acute myeloid leukemia (AML) burden and is characterizing the CD33-D2 isoform as a novel theranostic target for radiopharmaceutical therapy.

Revolutionizing Transplant and Gene Therapy

In collaboration with hematology and gene therapy teams, the Hui Lab is reshaping conditioning strategies for sickle cell disease and thalassemia. Organ-sparing TMI regimens enable successful engraftment, fertility preservation and reduced organ toxicity—outcomes validated in a first-in-human trial (NCT05384756). These advances are enabling safer, curative therapies for monogenic blood disorders.

Heavy Ion Therapy for Next-Generation TMI

Through collaborations with Osaka University and GSI Germany, the lab is investigating proton and carbon-ion radiation for marrow-targeted therapy. These high-linear energy transfer (LET) particles offer superior dose conformity and enhanced biological effectiveness, providing a strong foundation for next-generation conditioning regimens.

Building on principles established in hematologic malignancies, the Hui Lab applies precision radiation and immune modulation to solid tumors. In collaboration with Scott Goldsmith, M.D., the team is pioneering radiation-enhanced bispecific antibody therapies for extramedullary multiple myeloma (EMD), using radiation as an immune primer to improve antibody delivery, immune infiltration and tumor clearance. Through spatial transcriptomics, T-cell receptor sequencing and imaging-guided modeling, the lab identifies biomarkers predictive of treatment response and resistance.

The group also developed MIRRORS, the first small-animal PET-CT platform enabling biology-guided targeted radiotherapy and real-time visualization of radiation response.

In collaboration with John Shively, Ph.D., the lab demonstrated that image-guided stereotactic body radiation therapy (SBRT) combined with immune-checkpoint cytokine therapy enhances antitumor immunity, while SBRT paired with antibody α-therapy achieves durable local and systemic control. Partnering with Walter Tinganelli, Ph.D., at GSI, Germany, the team is advancing carbon ion therapy with immune checkpoint inhibition, defining a new paradigm of curative, regenerative radiotherapy built on biological insight and immune precision.