Prof. Rotem Karni

by Mai I. Baker

Prof. Rotem Karni is the Professor and Chair of the Biochemistry and Molecular Biology department at the Institute for Medical Research Israel-Canada, at the Hebrew University Medical School in Jerusalem, Israel. Prof. Karni’s research work is focused on understanding how alternative splicing is fundamental to the initiation and progression of some cancers. Throughout his academic career, Professor Karni has received multiple prestigious awards, including the Kaye Innovation Award, in 2021.

Professor Karni earned his Bachelor’s degree in Biology at the Hebrew University of Jerusalem in 1996. He then continued his graduate studies at the Department of Biological Chemistry, Institute of Life Sciences, at the Hebrew University in 1998. During his PhD work, Prof. Karni studied the oncogenic signal transduction pathways under the supervision of Professor Alex Levitzki. His graduate research birthed his passion for studying splicing in cancer. Prof. Karni recalled, “in one of the genetic screens I performed which was never published, I discovered a splicing factor that seemed to protect cells from apoptosis.” This remarkable finding sparked his curiosity for learning more about the role of splicing factors in cancer.  His extensive literature searches revealed that at that time very little was known about the role(s) of splicing factors and splicing regulation in cancer development and progression. Recognizing the importance of this knowledge gap, he decided that this understudied field would be the focus of his future research. Inspired by his passion for splicing, following his PhD, Prof. Karni moved to Prof. Adrian Krainer’s lab at Cold Spring Harbor Laboratory, NY in 2002 for his post-doctoral training. “Working in the Krainer Lab allowed me to combine my previous knowledge of cancer biology with what I learned from splicing experts, Adrian Krainer and his lab members. This synergy lead to the discovery of how the SRSF1 splicing factor acts as a proto-oncogene, and also opened up further studies on other splicing factors and their  regulators in cancer.” His post-doctoral training was not only scientifically fruitful, his time in the Krainer laboratory also taught him “how to approach a biological question by delving deep into the associated molecular mechanisms.” Additionally, “by working on a project which differs from the main focus of the lab,” Prof. Karni noted that he critically learned “how to reach out to other scientists for fruitful collaborations.”

“It is very exciting to see how the understanding of basic molecular mechanisms is the starting point of the long process to clinical application.”

Currently, the work in Prof. Karni’s lab is focusing on several projects. Among these projects they found that a splicing factor called RBFOX2 acts as a potent tumor suppressor in pancreatic cancer progression and regulates tumor invasiveness through its downstream splicing network. Additionally, their work has shown that synthetic induction of exon skipping via antisense oligonucleotides can cause frameshift mutations that generate neoantigens, which ultimately can expose the tumors to the immune system. One of Prof. Karni’s goals is “to translate the knowledge we gather into treatments for diseases.” He feels that “it is crucial that the biotech industry and the academic world collaborate” adding that “it is very exciting to see how understanding the basic molecular mechanisms would become the starting point of clinical applications.” To bridge the gap between the two sectors, Prof. Karni has “been involved in establishing three new biotech startups based on technologies that were developed in his lab.” He has been awarded several different patents on innovative technologies related to cancer treatment, and recently initiated a collaborative project between another biotech company and his lab.

One piece of advice that Prof. Karni shares with students is to “shift research fields and to apply the knowledge that you gained in one discipline to a different area of research.” In other words, he recommends leveraging your existing expertise to ask specific questions in a new field. He added, “I also strongly believe in collaborations and learning from others. Never hesitate to ask for help and to learn new technologies from others.” Prof. Karni recalls the biggest challenges, throughout his academic career.  “The greatest challenge was when I started as a postdoc in a splicing lab, knowing little about the mechanisms underpinning RNA splicing. I remember sitting in lab meetings on the topic of splice site recognition … and feeling that I knew nothing. It took me 2-3 years to feel that I understand what they were talking about.”  He cites these personal experiences as encouragement to trainees of all levels.  Simply, feeling out of your depth is normal, and can be overcome by careful study, reading, and dedication to your work.  His “second greatest challenge as a group leader was, and [continues to be], how to motivate lab members about their research projects even when experiments don’t work as expected.”  In particular, this challenge centers on motivating trainees, building their skills and confidence, and using that to maintain their optimism even in the face of bad results and failed experiments.”  

“Never hesitate to ask for help and to learn new technologies from others.”

Professor Karni finds the RNA Society as “a very unique community of scientists, dedicated to the idea of sharing ideas, mutual respect, and support. When compared to other research communities, I think the RNA Society is blessed to have these characteristics”.  Hence, he always enjoys attending the Annual Meetings of the RNA Society. “One of the most touching and memorable moments for me was to be present when my postdoctoral mentor, Prof. Adrian Krainer, received the Lifetime Achievement Award at the RNA Society meeting in Krakow, Poland in 2019. During his amazing and inspiring lecture, Adrian described the development of the first RNA drug that rescues the lives of children suffering from SMA.”

Unsurprisingly, his favorite RNA is actually a family of synthetic RNAs called Decoy oligonucleotides. Decoy oligonucleotides , “are oligonucleotides, developed in my team, that bind to the RNA recognition motifs of RNA binding proteins and inhibit the activity of specific splicing factors.” His favorite RNA journal article is “Regulated tissue-specific expression of antagonistic pre-mRNA splicing factors”, by Hanamura, A. et al. 1998. He described, “this paper, which has been cited more than 300 times since its publication, had a significant impact on my journey to understand the role of splicing factors in cancer.”

Professor Karni puts a great value on using social media to communicate his lab’s research findings. “I am active on LinkedIn, sharing papers and discoveries, as well as, technologies originating in my lab and interesting findings from other labs. I am also active (although less so) on Twitter.”  He continued, “I feel that I learn new things in the field directly from social media rather than searching the literature in more traditional ways.” You can find him on LinkedIn here, or on twitter @Karni_rotem, or you can visit his lab website here