by Tufts University

Dr. Cornelia Peterson calibrates a piece of equipment used to measure intraocular pressure during an ocular toxicity study in animals. Credit: Noah Moss

Dr. Cornelia Peterson is dedicated to finding treatments for cancer by researching tumors that develop in Meibomian glands, the specialized oil-secreting glands of the eyelid. She joined Cummings School of Veterinary Medicine at Tufts University's faculty a year and a half ago as an assistant professor of anatomic pathology in the Department of Comparative Pathobiology, establishing her own lab at Cummings School to advance research in comparative ocular pathology.

Four articles highlight the findings of her work, in the journals Orbit, International Journal of Molecular Sciences, Frontiers in Veterinary Science and Topics in Companion Animal Medicine.

Peterson's lab research concentrates on genes that cause tumors in the Meibomian gland. These tumors form when particular genes are uninhibited or overexpressed, and cells can become cancerous and metastasize. Her research is focused on better understanding these tumors and finding therapies to treat them effectively.

She explains, "My research efforts seek to elucidate mechanisms of eye diseases and visual system diseases, particularly neoplasms of the ocular surface and adnexa, with comparative tissue-based approaches."

Two of the four published manuscripts involve human Meibomian gland tumors, and two describe unusual cancer presentations in companion animals.

"The studies are all based on interesting features of cancers. The overall goal is identifying unique features of cancers to see if they can be exploited for more comprehensive treatment," says Peterson.

In collaboration with investigators she worked with during her postdoctoral fellowship in the Brain and Eye Tumor Laboratory at Johns Hopkins University, Peterson co-authored the case study, "Ocular adnexal sebaceous carcinoma in a patient with Li-Fraumeni syndrome," published in the July issue of Orbit.

A male patient at Johns Hopkins was diagnosed with ocular adnexal sebaceous carcinoma, a cancerous tumor of the Meibomian gland that often recurs and metastasizes, and multiple tumors in other parts of his body. Through subsequent testing, he was also found to have Li-Fraumeni syndrome (LFS), a genetic disorder caused by a mutation of the TP53 gene that increases the risk of several cancers.

This collaborative group had previously published a study in 2021 regarding a cohort of thirteen patients with ocular adnexal sebaceous carcinomas evaluated by similar genetic sequencing approaches. When this special case was presented at Johns Hopkins, the team decided to further examine the drivers of the tumor on the eyelid.

The patient's eyelid tumor was diagnosed as a tumor of interest, surgically removed, and submitted for genetic sequencing, revealing the mutation of the TP53 gene, a tumor-suppressor gene. He was treated with chemotherapy and radiation therapy and referred for genetic counseling. Several family members were also found to have various forms of cancer.

In terms of the significance of the case study's findings, Peterson explains, "From a clinical perspective, for ophthalmologists who see patients with tumors on the eyelid, if there is any history of prior or concurrent cancer elsewhere in the body, it should lower the bar for referral for genetic sequencing and counseling.

"It may not just be an isolated ocular cancer, but it may be arising because of a more systemic genetic syndrome. This has implications for the patient and their children as far as passing the mutation."

Publication of the study in Orbit will help raise awareness of their findings to the journal's audience of oculoplastic surgeons and other ophthalmologists. Peterson and her fellow investigators are continuing to test a cohort of tumors for TP53 mutations, and if any are found, they will pursue a case series with subsequent testing.

Featured in the September issue of the International Journal of Molecular Sciences, an issue dedicated to new cancer therapies, the research article titled, "Establishment and Characterization of Three Human Ocular Adnexal Sebaceous Carcinoma Cell Lines," co-authored by Peterson, was similarly a collaboration with her Johns Hopkins colleagues following up the 2021 study regarding ocular adnexal sebaceous carcinomas.

According to the report, "The pathology of this tumor remains poorly understood, and few models exist suitable for preclinical testing. The aim of this study was to establish new cell lines to serve as models for pathobiological and drug testing."

In the earlier study, the team analyzed fixed and stained patient tumor samples collected for clinical diagnosis. For this study, the investigators derived cell lines from tumor samples before clinical diagnosis to create cell lines (cell cultures that can be grown and last for an extended period of time for repeated testing) through a series of tests and genetic sequencing.

The investigators established three cell lines from the patients' ocular tumor tissues. In the 2021 study, the investigators found many tumors related to a dysregulated MYC gene, often associated with cancers. In this study, all cell lines showed significant amounts of MYC protein, indicating dysregulated expression of the MYC gene.

"The goal is to add to the literature," says Peterson. "Prior to our study, there were only two cell lines of this type of tumor anywhere, and now we have added three additional cell lines. We characterized genetic signatures within the tumors and cell lines and saw how they respond to different chemotherapeutic agents in culture.

"We established cell lines from the patient tumors, and we can treat those tumor cells with different agents in a dish before we treat animal models and then move on to human patients."

The investigators treated the cell lines with a form of chemotherapy that involves a glutamine metabolism inhibitor used previously to treat other tumors with high MYC expression, including pediatric brain tumors. In the cultured cell lines, this treatment decreased proliferation and increased death of the tumor cells with high expression of MYC, indicating a possible role for MYC-inhibiting therapies in these types of tumors to augment traditional chemotherapy and radiation therapy.

Peterson notes that if a tumor in a patient looks benign, that may delay diagnosis and treatment. Tumor cells may be located all around an eyelid, not only as part of the primary tumor mass. And while traditional chemotherapy is somewhat effective in this type of cancer, a mix of standard care chemotherapy with chemotherapy targeting MYC expression may be more effective.

Peterson is furthering research into the causes of increased MYC expression and how these cells survive, proliferate, and cause tumors. This work is ongoing in her lab at Cummings School, under the mentorship of Dr. Cheryl London, associate dean for Research and Graduate Education, Anne Engen and Dusty Professor in Comparative Oncology, and professor in the Department of Clinical Sciences at Cummings School, and Dr. Charles Eberhart, co-author of these two papers and professor of pathology and oncology and associate professor of ophthalmology at Johns Hopkins University School of Medicine.

Peterson's next two research studies derived from collaborations with students and faculty at Cummings School. While training students on rotation in Cummings School Veterinary Diagnostic Lab (CVDL), Peterson necropsied an animal with a curious presentation.

The patient came into the emergency room at Henry and Lois Hospital for Small Animals (FHSA) at Cummings School in respiratory distress, not an uncommon occurrence, but usually associated with primary heart muscle disease.

"Not every patient has what we expect it to have. This cat did not have primary heart muscle disease, he had lymphoma in the heart. Presentations don't always have a classic cause, sometimes there's a weird zebra," says Peterson. "This was also true for the fourth paper. The dog presented with neck pain, which is not what we would typically expect of a liver tumor with widespread metastases."

Two veterinary students were primary authors on these studies, "Case Report: Diffuse large B-cell lymphoma presenting as congestive heart failure in a cat" and "The peculiar clinical presentation and diagnostic results of a case of widely metastatic cholangiocellular carcinoma in a Siberian Husky dog," published respectively in the September issue of Frontiers in Veterinary Science and the November-December issue of Topics in Companion Animal Medicine.

Dr. Jake Johnson, V24, now a rotating intern at North Carolina State University Veterinary Hospital, was the primary author of the former, and Dr. Hannah Reichert, V24, currently a first-year anatomic pathology resident at the University of Pennsylvania, was the primary author of the latter.

"Increasing awareness that cardiac lymphoma and cholaniocellular carcinoma can present in unexpected ways can be helpful to clinicians and for guiding clinical research questions," says Peterson.

While Peterson's passion for research began as an undergraduate, her fascination with eyes and vision started early. She was born six weeks premature and was farsighted, so saw optometrists regularly from infancy and had corrective eye surgery when she was four years old. "I was always interested in how people could make my vision so much better."

Born and raised in Wyoming, Peterson earned her bachelor of science degree in zoology and later her D.V.M. at The Ohio State University. In her science courses, she always gravitated towards the wet labs. The summer before veterinary school, she worked in a lab investigating heat shock protein in a measles model, and while earning her D.V.M., she was a veterinary biosciences research assistant. She describes both experiences at Ohio State as very formative.

Peterson interned in small animal medicine and surgery at the University of Illinois at Urbana-Champaign, before returning to Ohio State's College of Optometry to pursue her Ph.D. in vision science and physiological optics. While earning her doctorate, she also worked as an emergency room veterinarian for six years to keep up her clinical skills.

She was offered a post-doctoral fellowship and residency in anatomic pathology at Johns Hopkins University School of Medicine, where she initiated the work related to the first two of the aforementioned published research studies.

In March 2023, Peterson established her own research lab at Cummings School. At the time, Cummings School was restarting the anatomic pathology service and looking to hire an anatomic pathologist with a clinical appointment. Peterson reached out to the chair of the Department of Comparative Pathobiology at Cummings School, Dr. Andrea Varela-Stokes, to express her interest.

"The fact that she heard me and took action showed that Cummings School does what's best for the people they want to bring in," says Peterson. "I have a lot of people on my side—research mentors, grant mentors, the department chair—fostering me to develop the independent research program."

This past summer, two Cummings School veterinary students in the Summer Research Program worked in her lab investigating various facets of her research on the MYC gene on the Meibomian gland in the eyelid.

Xiaochen (Sean) Yuan, V26 assessed the upstream drivers of MYC gene activation and the effects. Isabella Boyak, V27 studied how the increase or decrease of MYC expression impacts cell survival.

"When there's decreasing MYC expression, cells are more stressed and die. If increased expression, cells proliferate. We're looking at how that mechanism is working," Peterson explains.

Peterson recently connected with researchers at the University of Massachusetts to investigate similar signaling pathways in mouse models of breast cancer. "We have a whole group of veterinary pathologists here at Cummings School, and it's the beginning of a collaboration with medical doctors and researchers on the human side involved with animal models."

More information: Chia W. Hsu et al, Ocular adnexal sebaceous carcinoma in a patient with Li-Fraumeni syndrome, Orbit (2024). DOI: 10.1080/01676830.2024.2382268

Su-Chan Lee et al, Establishment and Characterization of Three Human Ocular Adnexal Sebaceous Carcinoma Cell Lines, International Journal of Molecular Sciences (2024). DOI: 10.3390/ijms251810183

Jake Johnson et al, Case report: Diffuse large B-cell lymphoma presenting as congestive heart failure in a cat, Frontiers in Veterinary Science (2024). DOI: 10.3389/fvets.2024.1467448

Hannah Reichert et al, The peculiar clinical presentation and diagnostic results of a case of widely metastatic cholangiocellular carcinoma in a Siberian Husky dog, Topics in Companion Animal Medicine (2024). DOI: 10.1016/j.tcam.2024.100923

Journal information: International Journal of Molecular Sciences 

Provided by Tufts University