Yaacov Richard Lawrence, MBBS
Project Title
Toward Precision Radiotherapy through Mitochondrial Manipulation
Named Grant
ICRF Rolfe Collaborative Project Grant for Pancreatic Cancer
About the Investigator
Dr. Yaacov Lawrence is a clinician-scientist in radiation oncology. His research focuses on the modulation of metabolic pathways during radiotherapy with therapeutic intent. He graduated from Cambridge University, UK and University College Hospital, London. Following clinical training in Jerusalem and Tel Aviv, he was a Fellow and subsequently Attending Physician at Thomas Jefferson University, Philadelphia. He has over 100 publications, has led numerous clinical trials and developed a new treatment that have been adopted worldwide. In 2023 he was appointed to chair the Benjamin Davidai Dep. Radiation Oncology, Sheba Medical Center.
About the Research
Radiotherapy (RT) is a powerful cancer treatment, but its effectiveness varies among patients due to differences in their ability to repair DNA, their handling of unstable molecules (free radicals), and immune system function. Recent discoveries highlight the importance of mitochondria—cellular structures that produce energy—in these processes. Mitochondria contain their own genetic material (mtDNA), which exists in different variants (‘flavors’). Dr. Lawrence’s co-investigator, Dr. Tal Yardeni, found that these variants influence immune system function.
Dr. Lawrence’s team believes that mtDNA variants, especially those in immune cells rather than tumor cells, play a crucial role in determining tumor response to radiotherapy. To investigate this, the lab will use specially developed laboratory mice that are identical except for their mtDNA. Through studies of pancreatic cancer in these mice, his team will examine how mtDNA variations affect: 1) Healthy tissue response to RT, 2) Pancreatic cancer cell sensitivity to RT and 3) The relative importance of immune cell versus tumor cell mtDNA in treatment response. If proven correct, this research could lead to groundbreaking cancer treatments. One approach would involve removing a patient’s immune cells, modifying their mitochondria to enhance the RT response, and returning these optimized cells to the patient. This could significantly improve RT effectiveness and pioneer new mitochondria-focused cancer therapies.