Research

Callie Berkowitz, MD is a classical hematologist and health services researcher committed to improving care delivery for patients with bleeding disorders and addressing the needs of women with abnormal bleeding. She is currently investigating clinical phenotypes and outcomes for patients with Bleeding Disorder of Unknown Cause with the goal of improving diagnostic and treatment pathways.

Patrick Ellsworth, MD is a physician scientist whose clinical focus is the transition from pediatric to adult care for adolescents and young adults with genetic blood disorders. His lab is focused on the interaction of endothelium and other cell surfaces with coagulation proteins. Using novel, in vitro techniques, his lab is evaluating the localization of FVIII mimetic therapies and how bleed treatment can be optimized by better understanding their mechanisms. He is also active in clinical research seeking to improve the treatment of acquired hemophilia A, as well as nonpharmacologic therapy of chronic pain in sickle cell disease.

Steven Grover, PhD. My group’s research is focused on identifying novel mechanisms responsible for pathological activation of coagulation and venous thromboembolism. Venous thromboembolism is a common cardiovascular disease and a major source of morbidity and mortality worldwide. To identify novel mechanisms, we leverage epidemiological, clinical sample and preclinical model-based approaches. We contend that a better mechanistic understanding will enable identification of at-risk populations and novel targets for the development of safe and effective anticoagulant drugs. The role of the natural anticoagulant C1-inhibitor in this setting remains an ongoing focus of our research.

Yohei Hisada, PhD is a basic scientist interested in the mechanisms of cancer-associated thrombosis and bleeding. Different types of cancer exhibit distinct mechanisms of thrombosis and bleeding. His research focuses on understanding the mechanisms of thrombosis in pancreatic cancer and bleeding in acute promyelocytic leukemia. His interests also extend to the mechanisms of thrombosis in other cancers, such as brain cancer and acute leukemia, as well as thrombosis and bleeding associated with cancer therapy.

Nigel Key, MB, ChB, FRCP serves as Director of the UNC Blood Research Center. His research interests range from basic laboratory studies of the interactions between blood cells and cellular organelles with the coagulation system, to large case-control and prospective cohort studies. Translational research interests include the vascular complications of sickle cell disease and sickle cell trait, and the contribution of hyperfibrinolysis to acute and chronic bleeding disorders. Dr. Key also actively participates in multicenter clinical trials, with a recent focus on gene therapy in hemophilia.

Jane Little, MD and Sam Wilson, MD lead the comprehensive adult sickle cell disease program at UNC. Sickle cell disease research at UNC focuses on understanding the changing adult sickle cell population in North Carolina and at UNC-Malawi. Ongoing work includes elucidating the mechanisms that underlie hypoxia in sickle cell disease (during pregnancy, with air travel, and when receiving chronic red blood cell transfusions). We are also investigating the use of multidisciplinary clinics to improve care and outcomes in sickle cell disease. We are members of the national Globin Research Network for Data and Discovery (GRNDaD) prospective registry for sickle cell disease. Our overall goal is to better identify and address the clinical challenges in adults living with sickle cell disease, while seeking to optimize care in the era of transformative and curative therapies.

Alice Ma, MD is the director of the adult Hematology/Oncology Fellowship Program.  Her research focuses on acquired bleeding disorders and new treatments for hemostatic diseases.

Nigel Mackman, PhD is a basic scientist interested in the mechanism of blood coagulation and the development of new safer anticoagulants. His research focuses on tissue factor, which together with is ligand Factor FVII/VIIa is the main activator of blood coagulation. The tissue factor-Factor VIIa complex plays an essential role on hemostasis. In addition, aberrant expression of tissue factor on monocytes during bacterial and viral infections leads to pathologic activation of coagulation, thrombosis and dissemination intravascular coagulation.

Micah Mooberry, MD serves as the Clinic Director for the UNC Benign Hematology clinic at Eastowne. His primary research interest is in venous thrombosis, including involvement in multi-center clinical trials of venous thrombosis treatment, as well as translational research.

Dougald Monroe, PhD is a biochemist and protein chemist working in the field of coagulation. His work focuses on the biochemical and cellular interactions of coagulation proteins with an emphasis on understanding the mechanisms behind therapies for hemophilia. This work includes constructing computational models of coagulation reactions to understand existing therapies and assist in development of potential new therapeutics.

Rafal Pawlinski, PhD,is the Research Associate Director of the UNC Comprehensive Sickle Cell program. His research focuses on understanding molecular and cellular mechanisms leading to the increased risk of prothrombotic complications associated with sickle cell disease and sickle cell trait. Using both animal models and clinical samples he seeks to identify potential strategies to attenuate/prevent these clinical complications.

Learn more on the UNC Blood Research Center website.

Learn more on the Bone Marrow Transplant and Cellular Therapy website.

The Leukemia Program encompasses a multidisciplinary group of Hematologists/Oncologists, advanced practitioners, nurse navigators, nurses, and research coordinators. The mission of the Leukemia Clinical Program is to provide the optimal experience and care for patients with leukemia and myeloproliferative neoplasms by providing shared decision making, patient-centered clinical care, and access to cutting-edge therapies and clinical trials for these conditions.

The Leukemia Program is at the forefront of investigating novel therapies to improve overall outcomes in patients with leukemia, myelodysplastic syndrome and myeloproliferative neoplasms. Led by Joshua Zeidner, MD, Associate Professor of Medicine, the Leukemia Program at University of North Carolina has a wide array of innovative clinical trials for patients with untreated/newly diagnosed acute myeloid leukemia (AML), relapsed/refractory AML, untreated/newly diagnosed acute lymphoblastic leukemia (ALL), relapsed/refractory ALL, untreated/newly diagnosed myelodysplastic syndromes (MDS), relapsed/refractory MDS, and chronic myeloid leukemia (CML).

Additionally, Brandi Reeves, MD, Assistant Professor of Medicine, leads the clinical and research program for myeloproliferative neoplasms (MPN’s) which includes clinical trials for patients with polycythemia vera, essential thrombocytosis, and myelofibrosis.

Lymphoma and Chronic Lymphocytic Leukemia Program

The lymphoma group has been very active in treating rare and underserved lymphoma subtypes. Highlights of our group include:

1. Lymphoma in elderly or frail patients.

• The lymphoma group has focused on several projects that specifically target effective treatment approaches in elderly or frail patients. Anne Beaven, MD is leading a study (S1918) evaluating oral azacitidine with R-miniCHOP for the treatment of DLBCL in patients over the age of 75. Anne Beaven, MD is also the national PI on a A052101, a clinical trial evaluating continuous vs intermittent zanubrutinib maintenance as initial therapy in older patients with mantle cell lymphoma.
• Additionally, Christopher Dittus, DO, MPH has an investigator-initiated trial (IIT) evaluating the targeted BTK inhibitor, acalabrutinib for the treatment of relapsed primary and secondary CNS lymphoma (LCCC1841). This study targets patients who are not eligible for more intensive chemotherapy options.

2. CAR-T cell therapy

• Most of the clinical CAR-T research has been led by Natalie Grover, MD in the lymphoma group. Areas of specific focus in lymphoma have been the CD30 CAR-T program, kappa CAR-T clinical trial for kappa expressing lymphomas, and the CD19 CAR-T trial using the inducible caspase 9 safety switch (LCCC1813) which has accrued CD19+ patients including Waldenstrom’s Macroglobulinemia.
• CD30 Program: This has led to a publication in JCO. This product has also received FDA RMAT (regenerative medicine advanced therapy) designation. We now have trials open in Hodgkin lymphoma and peripheral T cell lymphoma and are planning to open a trial in germ cell tumors as well.
• Inducible caspase 9 safety switch: We have CAR-T clinical trials using the inducible caspase 9 safety switch to mitigate life-threatening toxicities. We have a recent publication describing using the safety switch in one of our clinical trials.
• Solid Tumors: We are opening new trials with novel targets and approaches in solid tumors including a trial in GBM, lung cancer and head and neck cancers.

Chronic Lymphocytic Leukemia (CLL) and Richter’s Transformation

CLL is the most common adult leukemia and there are ~200,000 people living with this cancer today in the United States.  Deborah Stephens, DO joined the division in 2023 to build a clinical and research program for patients with CLL and Richter’s Transformation.  We are currently opening or have opened clinical trials for patients at all stages of this cancer, including watch and wait (or initial observation), first-line therapy, second-line therapy, and beyond.

Deborah Stephens, DO leads the SWOG National Cooperative Group Sub-Committee for CLL and is the international principal investigator for the SWOG cooperative group clinical trial S1925 the EVOLVE CLL Study (NCT04269902).  In this trial, early intervention is tested for patients with high-molecular risk CLL who would otherwise wait for disease progression to treat.

Christopher Jensen, MD has received a competitive grant from the CLL Society to continue his work to address cancer-related fatigue in patients with CLL.

We are investigating many novel agents for CLL and Richter’s Transformation and including next generation Bruton’s tyrosine kinase inhibitors and degraders, next generation BCL2 inhibitors, bispecific antibodies, and autologous and allogeneic CAR-T therapy.

Multiple Myeloma and Amyloidosis Program

The UNC Lineberger Multiple Myeloma and Amyloidosis Program is a highly active clinical entity serving patients across NC and surrounding states with plasma cell disorders.  The program also hosts a robust research effort aimed at improving therapies for patients with these disorders worldwide by devising cutting edge new medications, optimizing existing ones, and otherwise studying methods for improving care for patients.

The program is primarily based at the UNC Hillsborough Medical Office Building. This geography affords our patients the best of both worlds – all the advances of a subspecialty academic medical center, with the comfort and convenience of a small clinic.

Broadly speaking in terms of research, the program has a number of scientific initiatives. A few examples follow.

Clinically developing new agents and optimizing existing agents for treating plasma cell disorders:

UNC Lineberger physicians lead national efforts advancing the treatment of these conditions.  Sam Rubinstein, MD MSCI is chairing an NC-wide study (LCCC2323) of daratumumab, lenalidomide, bortezomib and dexamethasone in patients with newly diagnosed myeloma, testing a novel “real world” schedule for administering these medications that is likely more tolerable and convenient than standard approaches.  The study is one of the first of its kind in the US to utilize a “decentralized model,” which broadens its availability statewide, in recognition of the desire of many patients to be treated close to home and not repeatedly travel to UNC for their myeloma care.  Eben Lichtman, MD is leading a national study (LCCC2119) of isatuximab, pomalidomide and dexamethasone in older and frail adults with relapsed and refractory multiple myeloma.  The standard dosing for this regimen can be difficult on patients who are vulnerable to side effects, and this study is testing a reduced-dosing strategy geared toward preserving the regimen’s effectiveness in controlling myeloma while reducing side effect burden.  Sascha Tuchman, MD MHS is the chair for a nationwide study (A062102) in patients with relapsed and refractory myeloma who have been treated with idecabtagene vicleucel (“Abecma”) CAR-T, and then receive either a new medication called iberdomide or standard observation.  The study’s goal is to assess the safety of iberdomide in these patients, as well as the drug’s ability to enhance CAR-T’s ability to keep myeloma in remission for a longer period of time. Separately, Dr. Tuchman also leads the LCCC1603 study of a new CD138-directed chimeric antigen receptor T-cell (CAR-T) for the treatment of advanced myeloma.  This is a truly bench-to-bedside UNC creation: it was designed in the lab by UNC faculty Drs. Barbara Savoldo and Gianpietro Dotti, it is manufactured for patients at clinical-grade (“GMP”) UNC facilities, and it is being studied in a first-in-human clinical trial for patients in the UNC clinical program who need newer approaches.  UNC Lineberger is one of very few centers worldwide that has the ability to take something like this from discovery all the way to patients.

Laboratory-based efforts to deepen our understanding of disease biology and develop entirely new approaches for therapy:

Eben Lichtman, MD created the LCCC1849 (PERMIT) study in collaboration with UNC infectious disease physician Tessa Andermann, MD, to examine both immune system function and the gut microbiome (bacteria and other organisms that naturally live in the intestines) in patients with plasma cell disorders.  1) In patients with myeloma precursor conditions (monoclonal gammopathy of uncertain significance or smoldering myeloma), they aim to identify immune or microbiome predictors of development of multiple myeloma.  2) For patients with smoldering myeloma or active multiple myeloma on treatment, they seek to explore the same domains to find predictors of response to therapy and longer duration of remission.  Better understanding these areas will hopefully lead to the development of concepts regarding how to intervene in these areas in ways that improve clinical outcomes for patients.

The entire program is collaborating with UNC Lineberger physician scientist Dr. Chad Pecot, who is an internationally renowned expert in RNA therapeutics.  The group is working with Dr. Pecot and his lab to create first-ever types of new RNA-based approaches for suppressing the synthesis of key proteins in myeloma development, with the aim of devising chemotherapy-free approaches to treating these disorders. Once appropriate candidates are identified, they will be moved forward into the UNC clinics where they will be offered as part of research studies to patients needing new approaches.

Clinical correlatives to better understand the impact of plasma cell disorders and treatment on patients:

The entire program collaborates to run the LCCC1728 study and the separate but connected UNC plasma cell disease quality database.  These efforts conducted among patients being treated at UNC for any plasma cell disorder collect data from patients in such areas as quality of life, physical function, cognitive function, response to therapy and financial impact of treatment. The goal of this now 300+ patient and 5+ year effort is two-fold: 1) to provide objective data that ensures that the quality of clinical care for patients with plasma cell disorders at UNC is outstanding, and 2) to provide research data that enables the program to learn from our patients’ experience.  Multiple manuscripts have been published in the scientific literature using these data, which means that people worldwide with multiple myeloma and related conditions are learning from our patients and our work.