June 24, 2026

Dear Belinda

George Q Daley, MD, PhD | Dean of the Faculty of Medicine | Caroline Shields Walker Professor of Medicine

25 Shattuck Street, Boston, MA 02115 | t: (617) 432-1501 | e: George_Daley@hms.harvard.edu

I’m pleased to share this report on the Henri and Belinda Termeer Program in Systems Pharmacology at Harvard Medical School. Your support enables investigators in the Laboratory of Systems Pharmacology (LSP) to deepen our understanding of cancer, including its microenvironment and response to therapy, and to translate these insights into more effective treatments. 

The impact of the Termeer Program is especially evident in the work of three LSP scientists, each of whom works closely with colleagues across our affiliated hospitals. Dr. Caitlin Mills is defining how polypharmacology shapes the action of kinase inhibitors in cancer and neurodegeneration—work that is informing both the development of new drugs and the optimal use of existing therapies. Dr. Kristin Qian is using advanced multiplexed imaging and spatial biology to map the tumor-immune microenvironment in colorectal cancer and to identify spatial biomarkers of progression and therapeutic response. Dr. Alyce Chen is strengthening the LSP’s partnerships with Mass General Brigham and leading a new collaboration with Danaher Corporation to bring the LSP’s tissue imaging technology into clinical practice. Together, these scientists also play important roles in training and supporting students, postdoctoral fellows, and early-career staff.

Thank you again for establishing the Termeer Program and for your dedicated service on the Board of Fellows. I remain deeply grateful for your continued support and for all that you do to advance the School’s mission.

Research Highlights

Research interests

• ​​Prediction of breast and ovarian cancer drug response response
  
  

• Kinase inhibitor polypharmacology
  
  
• High-throughput phenotypic screening

Mentorship

• ​​Dr. Mills mentors graduate students and early-career technicians in the lab.

Caitlin Mills, PhD 

• ​​Director of Preclinical Pharmacology, Harvard Program in Therapeutic Science
  
  

• Lecturer on Systems Biology, Harvard Medical School 

Titles

assembly of a practically scaled Optimal Kinase Library (OKL), a collection of diverse (in terms of assigned targets and chemical structures) small-molecule kinase inhibitors that Dr. Mills and her colleagues have fully annotated and implemented in experimental workflows. By detailing the affinities of OKL inhibitors for all kinases, Dr. Mills has found that polypharmacology is as prominent in clinically approved drugs as in molecules that failed to progress through trials, and that it has remained a feature of kinase inhibitors over decades of development. This finding suggests that targets beyond those intended to be inhibited likely contribute important effects in both laboratory and clinical settings. Dr. Mills was invited to speak about this work at the annual Society for Laboratory Automation and Screening meeting in February and has recently submitted this work for publication. 

Collaborations built around deconvolving the polypharmacology of kinase inhibitors with promising preclinical profiles in neurodegeneration have advanced over the past year. Working with Veselina Petrova, PhD, and Clifford Woolf, MB, BCh, PhD, at Boston Children’s Hospital, Dr. Mills is investigating chemotherapy-induced peripheral neuropathy (CIPN). With Mark Albers, MD ’95, PhD ’95, a core LSP faculty member and neurologist at Massachusetts General Hospital, she is pursuing new targets in Alzheimer’s disease (AD).

In CIPN, the team’s work uncovering MAP4 kinase inhibition as neuroprotective against paclitaxel in sensory neurons was recently accepted for publication. Importantly, Dr. Mills found that inhibition of the same kinases does not interfere with paclitaxel’s desired killing of cancer cells, thus showing a promising therapeutic window.

In AD, the Albers Lab previously reported that cytoplasmic double-stranded RNA (cdsRNA) is coincident with TDP-43 aggregates and leads to neuroinflammation and cell death. Differentiated neurons can be treated with a mimetic of cdsRNA to model this subset of AD patients with TDP-43 pathology. Using this model, Dr. Mills applied the fully profiled OKL inhibitors described above to screen for novel targets. Screening hits were found to share kinase targets involved in multiple pathways that have been linked to neurodegenerative diseases, including endosomal transport and autophagy. Hypotheses generated from the primary screen are currently being tested.

Dr. Mills has also continued to collaborate with Nathanael Gray, PhD, of Stanford University and Panos Konstantinopoulos, MD, PhD, MMSc ’10, of Dana-Farber Cancer Institute to explore the potential of CDK7 inhibition for treating ovarian cancer. The utility of targeted therapies is often limited by resistance, either frank or acquired. In the last year, Dr. Mills has integrated omics data from:

• Thirty ovarian cancer cell lines with variable baseline responses to CDK7 inhibition.
• Ovarian cancer cell lines with acquired resistance to CDK7 inhibitors.
• Whole-genome CRISPR screens to gain a comprehensive view of determinants of response to CDK7 inhibition. 
  

These analyses have pointed to the involvement of a specific protein complex, as evidenced by recurrent gene expression changes and induced genetic mutations. Dr. Mills is actively working to validate these results and gain a better understanding of how the two are related at the molecular level. Together, she hopes that these studies will help elucidate how best to leverage CDK7 inhibition for therapeutic gain, with the specific goal of determining how CDK7 can be optimally combined with other targeted therapies or chemotherapeutics. Dr. Mills is also collaborating with the Gray Lab on novel degrader and glue molecules. A collaboration on a CDK6 degrader is currently under review and includes phenotypic effects measured by Dr. Mills’ team in models of acute myeloid leukemia and glioblastoma. 
 

Caitlin Mills, PhD, joined the Laboratory of Systems Pharmacology (LSP) at Harvard Medical School in the fall of 2014 to further pursue her interest in breast cancer research. Since uncovering important functional secondary targets of CDK4/6 inhibitors, a breakthrough family of drugs for recurrent hormone-positive breast cancer, she has expanded her research program to new drug classes and disease contexts. 

Dr. Mills continues to be driven by a desire to uncover and understand the contributions of polypharmacology. She has worked extensively to profile the multi-targeting nature of kinase inhibitors.This project began with the 

Kristin Qian, PhD ’23, joined the LSP in the summer of 2023 as a postdoctoral research fellow. She currently leads the colorectal cancer (CRC) research efforts at the LSP and studies the tumor-immune microenvironment of CRC progression using single-cell spatial biology methods, integrating multiplexed tissue imaging, spatial statistics, and computational biology to analyze pathology images and quantify tissue geographies. 

In the clinic, patients with CRC are typically stratified by DNA mismatch repair (MMR) status; for example, immunotherapy has emerged as a promising treatment for patients with deficient mismatch repair (dMMR). However, MMR status alone does not fully predict therapeutic response, as a recent trial has demonstrated response in patients with proficient MMR (pMMR). Dr. Qian and her colleague Jeremiah Wala, PhD ’17, MD ’19, of Dana-Farber Cancer Institute, have recently defined a distinct T-cell-infiltrated pMMR (ti-pMMR) subset of pMMR tumors that exhibit CD8 T cell infiltration levels comparable to those in dMMR tumors. She has further shown that these ti-pMMR tumors are abundant in activated PD1+ Granzyme B+ cytotoxic T cells that are in direct contact with the tumor epithelium, as well as in immune clusters enriched for TCF1+ progenitor-exhausted T cells and expanded regulatory T cell populations, consistent with an active yet controlled anti-tumor immune response. These results demonstrate that this ti-pMMR subtype of CRC is immunologically active and motivate the consideration of immunotherapy strategies in this population. She expects to publish these findings soon. 

• ​​Dr. Qian organizes a weekly colorectal cancer working group for the lab, inviting graduate students, postdocs, and senior scientists to engage in dialogue about the current state of the field, research updates, and technology development to help advance related projects at the LSP.  
  

Collaboration

Research interests

• ​​Spatial organization of immune infiltration in cancer
  
  

• Colorectal cancer progression and early detection
  
  

• Tumor microenvironment and cellular networks

   

• ​​Postdoctoral Research Fellow, Laboratory of Systems Pharmacology 
  

Title

Dr. Qian is also interested in understanding the CRC progression axis, especially as the prevalence of early-onset disease increases. To better assess the risk factors and spatial determinants of progression in polyps and adenomas from patients with and without subsequent CRC diagnosis, she is collaborating with Mingyang Song, MBBS, SM ’14, SD ’15, at the Harvard T.H. Chan School of Public Health, and Michael Drage, MD, PhD, at Massachusetts General Hospital. Over the past few months, she has examined colorectal polyps from cohorts of patients with matched CRC tumors, as well as polyps from healthy patients, to identify changes in the immune, epithelial, and stromal compartments between samples, with the goal of better understanding the underlying morphological and cellular transformations involved in cancer progression. 

Her work on spatial profiling of immune components in CRC tumors has also led to collaborations with Marios Giannakis, MD, PhD, at Dana-Farber Cancer Institute, measuring dysfunctional natural killer cells in RNF43-mutated dMMR CRC tumors, as well as with clinicians at Johns Hopkins University to analyze CRC liver metastases pre- and post-treatment from a PI3K-inhibitor/anti-PD-1 combination therapy trial. These projects are currently under review and near publication. 

Dr. Qian is also an active contributor in other cross-institutional collaborations, including unique projects with Michael Snyder, PhD, and Christina Curtis, PhD, at Stanford University to explore an integrative 3D reconstruction of both the normal human colon and CRC tumors using multiplexed imaging and spatial transcriptomics, and to study CRC brain metastasis and organotropism, respectively. 

Ultimately, she hopes her work will contribute to new insights into colorectal cancer tumor subtypes, progression, and drug response prediction. The imaging-based spatial profiling methods used in this work also have the potential to be used as a diagnostic. Dr. Qian hopes that her research will provide the basis for the development of new or improved prognostics and predictive biomarkers for stratified trials and patient care. 

Kristin Qian, PhD ’23 

Research Highlights

CRC continues to be a leading cause of cancer-related mortality globally. Dr. Qian is interested in mapping the tumor microenvironment and architecture of these tumors to discover novel spatial features and interactions that could serve as better biomarkers or prognostic indicators. To do this, she leverages fundamental tools developed in the LSP, such as cyclic immunofluorescence (CyCIF) and the Orion multiplexed imaging platform for high-throughput analysis of whole-slide imaging of tissues from patients with CRC. (Read how Orion offers deeper insight into a tumor’s type, behavior, and likely response to treatment.) Dr. Qian also works closely with microscopists and technology developers at the LSP focusing on 3D high-resolution tissue imaging in addition to deep 2D high-plex imaging, including key contributors Jia-Ren Lin, PhD, Clarence Yapp, DPhil, and graduate student Daniel Lu.

This year, support from the Termeer Program enabled Alyce Chen, MPH, PhD ’12, to further strengthen the LSP’s partnership with colleagues across Mass General Brigham. A major focus of these efforts was the submission of a National Cancer Institute Program Project (P01) grant application with Genevieve Boland, MD, PhD, of Massachusetts General Hospital; Christine Lian, MD, of Brigham and Women’s Hospital; and David Liu, MD, of Dana-Farber Cancer Institute. The LSP plans to submit multiple National Institutes of Health Research Project (R01) grant proposals and private foundation grant proposals with the same team this year. 

​Dr. Chen also managed a new collaboration with Danaher Corporation, a global diagnostics and life‑sciences company, that aims to bring the LSP’s tissue-imaging technology into the clinic to further advance personalized medicine. The initial phase of this project focuses on PD-L1 protein expression in lung cancer; additional collaborations with Danaher will expand the focus to other disease areas. This collaboration is an incredible step toward bringing the LSP’s technology into clinical practice.

Termeer Program support has also enabled Dr. Chen to mentor early-career data managers—a growth opportunity she describes as incredibly rewarding. She notes that the LSP’s two data managers are critical to the life cycle management of the lab’s data, especially its tissue-imaging data. As the partnership with Danaher grows, data integrity will be essential, and Dr. Chen says she’s happy to be a guiding influence for the team.

Key Role

Title

Interests

• ​​Cancer initiation and progression
  
  

• Science communication 
  

• Cyclic Immunofluorescence (CyCIF) program and award management
  

• ​​Dr. Chen serves as principal investigator for Gray BRCA Pre-Cancer Atlas informatics. In this role, she develops and deploys the computational and informatic components required to support the Atlas, a pioneering digital resource for data on early-stage breast and ovarian cancers.
  

Alyce Chen, MPH, PhD ’12

• ​​Scientific Program Manager for the Laboratory of Systems Pharmacology 
  

Highlights