First Person is a series of interviews with the first authors of a selection of papers published in Biology Open, helping researchers promote themselves alongside their papers. Latasha Ludwig is first author on ‘ Patient-matched tumours, plasma, and cell lines reveal tumour microenvironment- and cell culture-specific microRNAs’, published in BiO. Latasha conducted the research described in this article while a PhD student in Geoffrey A. Wood's lab at the Department of Pathobiology, Ontario Veterinary College, University of Guelph, Canada. She is now an assistant clinical professor at the Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, USA, investigating canine and feline tumour pathology, including microRNAs as prognostic and diagnostic biomarkers.

Latasha Ludwig

Describe your scientific journey and your current research focus

I began my scientific journey as a veterinary student interested in pathology and research in general. Throughout my Doctor of Veterinary Medicine training, I spent time in multiple pathology research labs investigating both Johne's disease in cattle and canine osteosarcoma and mammary carcinoma. I gained a particular interest in canine oncology from this work. With my interest in pathology, I pursued a combined PhD program with Dr Geoffrey A. Wood, which included practical training towards board-certification in veterinary anatomic pathology. My PhD focused on microRNAs and their potential to serve as diagnostic and prognostic markers in tissue and blood of multiple canine cancers. I additionally pursued collaborative research projects involving genomic sequencing in canine and feline tumours, and projects developing and analysing immunohistochemical markers. Today I am board-certified with the American College of Veterinary Pathologists and successfully defended my PhD prior to beginning a clinical track assistant faculty position at Cornell University. Here I can combine my research interests in broad aspects of canine and feline oncology, along with serving the community as a diagnostic pathologist and mentor to residents and veterinary students.

Who or what inspired you to become a scientist?

As with most veterinarians, I developed a love for the care of animals. However, I enjoyed the discipline of pathology as it seemed ‘they always had the answers’. I have learned since that this is not necessarily the case, but pathology develops an extensive curiosity and drive to ‘find the answers’. This passion to help patients practically but also have a greater understanding of disease drove my interest in becoming a scientist. I hope to continue to research and better understand the diseases that afflict patients seen through our diagnostic service to ameliorate their quality of life and prevent disease in the future.

How would you explain the main finding of your paper?

MicroRNAs are small molecules present in cells and bodily fluids. Over several decades, microRNAs have shown their potential as both diagnostic and prognostic biomarkers in blood and tissue. Cell culture has been utilised extensively to better understand how they work. Additionally, this modality has been utilised to test the potential role of microRNAs as therapeutics. However, it seems in the vast majority of cases these therapeutics are relatively unsuccessful when moving out of the culture plate and into animal models. MicroRNA experiments have been performed in all three of these sample types independently and increasing studies are looking at both the blood and tissue profiles as diagnostic and prognostic markers of disease. To our knowledge, no study has investigated how the expression of microRNAs may differ across these three sample types within from the same patient. Dogs are an excellent model for many human diseases as they share the same environment and have a shorter lifespan. This includes osteosarcoma, a type of bone cancer, which is much more common in dogs than people. We looked at blood, tissue, and cell line samples from the same dog that had osteosarcoma to investigate how these sample types may differ in their expression of microRNAs. We found that some microRNAs are highly expressed in all sample types while others appear to be very specific to the sample type of interest. These differences should be considered when performing specific sample type experiments to not over-interpret a finding and lead to inappropriate use of that information in more complex studies.

What are the potential implications of this finding for your field of research?

This research provides a foundational knowledge and list of microRNAs that are likely associated with the tumour microenvironment and cell culture environment and not necessarily the disease process in canine osteosarcoma. More broadly, it provides evidence that these samples are different in the microRNAs that they express and so information from cell culture experiments should not be over-interpreted as these findings may not translate to tissue samples and beyond. As previously mentioned, dogs are an excellent model for osteosarcoma and microRNAs are highly conserved across species. So, these results have the potential to translate to human studies.

Working in a team and with people that have differing expertise is rewarding and I believe it enhances projects to approach questions in a multi-faceted way

Cell culture (left) and H&E histology (right) of canine primary appendicular osteosarcoma. Note the stromal, osteoid (arrow), and vascular (arrowhead) components present in whole tissue (histology) compared to only osteoblasts present in cell culture. These differences are reflected in the microRNA profiles. Cell culture image courtesy of Emma Vanderboon.

Cell culture (left) and H&E histology (right) of canine primary appendicular osteosarcoma. Note the stromal, osteoid (arrow), and vascular (arrowhead) components present in whole tissue (histology) compared to only osteoblasts present in cell culture. These differences are reflected in the microRNA profiles. Cell culture image courtesy of Emma Vanderboon.

Which part of this research project was the most rewarding?

I enjoyed most collaborating with Emma Vanderboon and Dr Courtney Schott to determine associations between proliferation and the cell lines of interest. Working in a team and with people that have differing expertise is rewarding and I believe it enhances projects to approach questions in a multi-faceted way. Particularly, determining that miR-34a-5p correlated with doubling time of the cell lines was interesting as this matched findings in the literature. So, it was very rewarding and exciting to see the ‘pieces of the puzzle’ coming together.

What do you enjoy most about being an early-career researcher?

I enjoy the limitless potential and opportunities for growth as well as the chance to still evolve as my research interests develop and change. I have had excellent mentors throughout my career thus far and being not so far removed from their tutelage allows me to maintain a close relationship and continued mentorship while branching out.

What piece of advice would you give to the next generation of researchers?

Be curious and don't be afraid to bring ideas forward to your advisor/principal investigator. Bringing forward my ideas and working together to acquire funding and develop projects has led to my most fulfilling work.

What's next for you?

I am currently an assistant clinical professor in anatomic pathology at Cornell University, landing my dream career in an academic institution where I can combine my diagnostic expertise in pathology, teach both residents and veterinary students, and perform research that I am passionate about. I plan to continue to collaborate on projects involving microRNAs and further investigate biomarkers in canine and feline oncology. I look forward to maintaining previously developed relationships in research and creating novel ones to expand my horizons. I hope in the end to make a valuable contribution to the veterinary community to improve patient care and quality of life of our furry friends.

Latasha Ludwig's contact details: Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, 240 Farrier Road, Ithaca, NY, USA 14853.

E-mail: [email protected]

Ludwig
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L.
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Vanderboon
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E. N.
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Treleaven
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H.
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Wood
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R. D.
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Schott
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C. R.
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Wood
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G. A.
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2024
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Patient-matched tumours, plasma, and cell lines reveal tumour microenvironment- and cell culture-specific microRNAs
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Bio. Open
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bio060483
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