9-14-23 entire issue hi res

The Corne¬ Daily Sun

The Cornell Daily Sun has been an independent newspaper serving Cornell’s community since its foundation in 1880 and has continued to be enjoyed by Cornellians and Ithacans alike.

With the oldest continuously independent college daily’s 143rd anniversary commencing on Sept. 16, The Sun compiled the history of its founding, its growth and the legacy its alumni have left.

1880: The Sun Rises for the First Time

On Sept. 10, 1880, Editor in Chief William Ballard Hoyt 1881 and The Sun’s first editorial board released a notice to all Cornell students. The letter announced the inception of an independent newspaper dedicated to publishing exclusive college news.

“Our books contain pledges enough already for advertisers, alumni and other former students, to pay every dollar of our expenses for the year, and we are, therefore, sure not to come to an untimely death,” the notice stated.

Six days later, the first edition of the Cornell Sun was published.

The first copy of The Sun was eight pages and measured nine inches by 12 inches. No

editors' names were listed. Eight pages was twice the size of a standard newspaper at the time and marked a bold heritage for The Sun, according to Robert Quick ’29, who was a senior editor in 1928.

“The [first copy of the Sun] gave the impression that The Sun was a noxious upstart — newspapers were hardly respectable anyway — and that all good people should avoid it,” Quick wrote in “A Half Century at Cornell,” a compilation of stories honoring the first 50 years since the paper’s founding.

The Sun’s first business manager, George F. Gifford 1880, printed the early Sun copies in the Andrus and Church Store in downtown Ithaca. He was also in charge of setting up the type, looking after the copy distribution and soliciting merchants in Ithaca.

While receiving subpar reviews in Ithaca, some daily papers described The Sun’s early copies as “bright” papers that “shine for the first time on the college world” and have “glowing promises.”

George Beebe 1882 recalled his time on The Sun’s first editorial board in “A Half Century at Cornell.” With a Cornell student body as small as 384, editors initially found generating content to be difficult.

A presidential election in 1880 was one of the first opportunities for The Sun to report

breaking news content. The first editorial board worked through the night —- recruiting as many Cornell students as possible —to be the first paper to inform Ithaca about the election result.

“Each fraternity member of the staff dug up all the news he could get about the men of his society, which gave us an unfailing supply of personals,” Beebe wrote. “After

a few weeks, it became apparent that the paper will succeed and we had no fear for the future.”

None of the original editors thought the paper would last even 50 years, according to Hudson P. Rose 1884, who was the freshman editor at the time.

Sen. Lea Webb (D-N.Y.) introduced legislation on May 23 that would allow the College of Agriculture and Life Sciences to manufacture wine, beer, spirits and cider. As of June 6, the bill is currently headed to the office of Gov. Kathy Hochul for approval.

Senate Bill S7085 authorizes the manufacture of beer, spirits, cider, wine and mead at the University through the CALS at Cornell and CALS’s New York State Agricultural Experiment Station,

which operates out of Geneva, New York. The bill also allots the same rights to Broome Community College in Binghamton.

The legislation would expand the abilities of the Cornell Craft Beverage Institute to include alcohol production and distillation.

Chris Gerling, extension associate at CCBI, specified that the Institute’s main focus is to provide opportunities for hands-on learning, emphasizing that the ability to partake in the production process would greatly benefit students in the Viticulture and Enology major.

“We want to make sure that

students have the opportunity to do hands-on learning, to actually produce products when they're doing their labs or their assignments,” Gerling said.

Gerling also stressed that passing the legislation would not drastically change the curriculum of those students already pursuing degrees in the subject area, but rather would allow them to move from a theoretical approach to a more practical and pragmatic form of learning.

It's notoriously challenging to earn Gordon Ramsay's approval, but after enduring weeks of intense food and business-related competition, former Cornell student Chris Kanik ’05 walked away with $250,000 and further motivation to propel his sustainability-focused company, Smart Cups, to greater heights.

“The last two weeks have been absolutely crazy,” Kanik said, having received an outpour of support following his success on the show. “[Competing in ‘Food Stars’] was the hardest thing I've ever done in my life — I’ve got a business, staff, a family. But my eye was on the

prize.”

“Gordon Ramsay's Food Stars” follows 15 aspiring food entrepreneurs competing for a chance to win the $250,000 investment and a business partnership with Ramsay. Contestants faced various challenges spanning branding, marketing, time management, hospitality, advertising and quality control. They also received guidance from guest experts, from Uber and UberEats CEO Dara Khosrowshshi to social media star MrBeast.

“Your product could quite honestly change the world,” Ramsay told Kanik during the Aug. 16 season one finale. “I want to be part of that journey with you — right by your side.”

Thursday, September 14, 2023

A LISTING OF FREE CAMPUS EVENTS

Today

Lavine, Pulsed-Power Research at the Cornell Laboratory of Plasma Studies

10 a.m. - 11 a.m., 233 Phillips Hall

S.C. Tsiang Macroeconomics Workshop: Ernest Liu

11:35 a.m. - 1:15 p.m., 498 Uris Hall

Cornell University Career Fair Days - Day 2: All Industries Noon - 5 p.m., Virtual Event

Midday Music: D.A. Mekonnen and Ravish Momin

12:30 p.m - 1:10 pm, B20 Lincoln Hall

“Decoding the Genomic Program to Generate T Cells” With A.D. White Professor-At-Large Ellen Rothenberg

4 p.m., College of Veterinary Medicine Lecture Hall 5

Performing and Media Arts at Sundance 2024 4:30 p.m., 220 Schwartz Center for the Performing Arts

Looking Back at Generations of Sun

inception.

The Sun’s First 50 Years

The first version of the linotype machine was invented in 1885, marking a large step forward in the journalism field. It allowed editors to mass produce papers at a quicker rate than ever before.

To do so, editors used a combination of linotype and other industrialized methods to print the “type,” or words and images compiled on the paper, on a continuous sheet of paper. The newspaper business became an industry, according to Frank E. Gannett 1898, who was on The Sun editorial board from 1896 to 1897.

“Out of it all there came to be the big modern newspaper, full of news, illustrations and advertising, all produced at a low cost, and sold to the public for a few cents a copy,” Gannett wrote in “A Half Century at Cornell.”

After his time at The Sun, Gannett founded the Gannett Company, which owns USA Today and directs the third largest newspaper group in the United States, and he received high praise from President Livingston Farrand, Cornell’s president at the time.

The Sun grew to be Ithaca’s only morning newspaper and a reputable source recognized by Cornell administration and major players in the journalism field. Nine years into its founding, The Sun received an invitation from Joseph Pulitzer to attend the New York World building opening in New York City. The New York World was published from 1860 until 1931 and pioneered sensationalist journalism by reporting on controversial topics. For The Sun, the invite marked a precedent for both its reputation and expansion.

The early 1900s and 1910s were met with great expansion, with The Sun establishing an office at The Ithaca Journal in Spring 1912 and appearing as “Ithaca’s Morning Newspaper” that fall. Female students also joined the editorial board in the midst of World War I. Harriot Parsons 1919 and Alice Street 1919 led as women’s manager and women’s editor.

World War I prompted a decline in editors and The Sun’s first publishing hiatus since its

“The Cornell Daily Sun will not resume publication with the opening of the college year 1918-1919 because of conditions created by the nation’s war preparations,” a pamphlet announced to the Cornell community.

Following World War I, The Sun struggled to rebound from its losses but passed a profitable year in 1928. At this point, Cornell Daily Sun had been changed to its modern name, The Cornell Daily Sun, after the 1927-1928 editorial board made the official change in the masthead and page captions.

The 1940s to the 1970s

This financial success carried into The Sun’s next 50 years. Much of its revenue was earned from both advertisements and subscriber fees.

“Based upon the number of ads that had been sold to The Sun on any given day, we would figure out how many pages the paper would be,” said Richard Morse ’70, business manager of The Sun in 1969. “Then we would tell the News department.”

Due to the well-established expectation for quality journalism throughout its next 30 years, it trained editors to be successful in the industry. Numerous editors and staff members grew to be large faces in the journalism field, despite the fact that Cornell does not offer a journalism major.

For example, Kurt Vonnegut ’44, a world renowned writer of the 20th century, served as an assistant managing editor and associate editor at The Sun during his time at Cornell University.

Though Vonnegut left Cornell to enlist in the army, his time with The Sun forever altered his life. Vonnegut became a famous author, publishing a wide array of literature including novels, short stories, nonfiction and plays. His book “Slaughterhouse-Five” earned a spot on the New York Times bestseller list in 1969.

Vonnegut credited The Sun as having provided him with a sense of purpose in his life.

“The Cornell Sun, thank goodness, showed me what to do with my life, and I did it,” Vonnegut remarked during a speech given at The Sun’s 125th anniversary dinner in 2005.

CALS Alcohol Production Pending Permission for Educational Use

Continued from page 1

“This isn’t going to bring about any kind of seismic change that we’re doing now. It’s just going to allow us to make sure that everything we are doing is both hands-on and in compliance with all regulations,” Gerling explained.

However, Gerling said the term manufacturing is used very loosely and explained that there will not be a commercial use for the public or mass production of alcoholic beverages. Instead, he said there will most likely be small demonstrations produced for small-scale quality control. Herling explained that CCBI also engages in grape breeding efforts to help local wineries in the region improve their cultivation methods and select grapes better suited for the climate.

“We have an experimental license, so we’re not this is not for any kind of commercial thing,” Gerling said. “This is all research [and] teaching.”

Webb, the bill’s sponsor, said she hopes the legislation will further the mission of land-grant colleges like Cornell to contribute to research and development in the agricultural industry of the state and the region.

“This legislation would ensure that Cornell CALS in Ithaca, the NYS Agricultural Experiment Station in Geneva, along with SUNY Broome, have the same protection that other higher educational institutions have received through the State Liquor Authority to enable these institutions to continue their research,” Webb wrote in a statement to The

Sun. “[This] is an important service to the farm-based beverage community, as well as educating the next generation of brewers, distillers and vintners through culinary arts training.”

The legislation is now headed to Hochul’s desk where, if signed by the governor, it will become law. Julie Suarez, associate dean for Land Grant Affairs at CALS, told The Sun CALS has asked Hochul to sign the legislation.

“Cornell CALS and Cornell AgriTech have a long history of providing research, teaching and extension expertise to the craft beverage community and farmers growing for craft beverage markets,” Suarez wrote in a statement to The Sun. “This new licensure category will help increase our abilities to provide students with hands-on access to the art and science of craft beverage production in Ithaca and Geneva. Cornell CALS and AgriTech value the support that Gov. Hochul has provided to the craft beverage community and have asked that she sign this legislation into law.”

Gerling emphasized the importance of the legislation in advancing students’ professional development and knowledge of their desired fields of study.

“We want them to be able to use the equipment, we want them to be able to analyze their own products, we want them to be able to see the outcomes of their choices,” Gerling said. “We want them to be able to really experience these processes that are being taught.”

to explore governmental and political fields. Throughout the 1960s, The Sun was recognized across the country, and college journalism was a powerful connector to U.S. governmental positions of authority. Alan Flaherty ’62, who was The Sun’s editor in chief in 1962, shook hands with two U.S. presidents during his time as an editor.

“The first one was Harry Truman, who was here on a relatively brief residency,” Flaherty said. “Because of my Sun position, I was part of one of the small groups that had conversations with him around in a seminar. And then with [John F.] Kennedy, the State Department [in Washington D.C.] invited a number of college editors to hear about U.S. policy of all sorts of things. I accepted the invitation as editor of The Sun.”

For Flaherty, The Sun opened up other opportunities he believed he would not have had otherwise. As editor in chief, he had exclusive access to interviews with notable Cornell alumni. He took his first airplane ride on account of The Sun to have the first opportunity to interview Wisconsin representative Henry Royce ’37.

“John Summerskill, who was the [Vice President] for Student Affairs, came up to me and said, ‘What are you doing Sunday afternoon?’” Flaherty said. “And I said, ‘Well, what do you have in mind?’ And he said, ‘Henry Royce is coming to speak at Cornell

and we’re sending a plane for him to pick him up in Detroit. Would you like to go and have a chance to talk to him on the way back?’ That was an easy question to answer.”

The 1940s to the 1970s also marked an increase in political coverage. Ed Zuckerman ’70, the Sun’s editor in chief in 1970 and a novelist, journalist and television writer and producer, oversaw many of the controversial political and University news the paper covered.

“The paper would consist of our locally generated stories by us and general international and national news stories off the A.P. machine,” Zuckerman said.

Zuckerman also recalled how the topic of the Vietnam War was frequently covered by The Sun, weighing heavily on many students’ lives, including his own.

“There was always news about the Vietnam War and President Johnson,” Zuckerman said. “The draft was still going on, and you really didn’t want to get drafted and sent to Vietnam for obvious reasons.”

To continue reading this story, please visit wwww.cornellsun.com.

Marisa Cefola can be reached at mcefola@cornellsun.com. Breanna Ferreira cam be reached at bmm223@cornell.edu.

Smart Cups Founder Wins Big

Founded by Kanik in 2017, Smart Cups employs a unique, novel approach of printing water-based products directly onto surfaces, aiming to advance sustainability and reduce waste in consumable products. This concept has been termed active ingredient printing.

“Our method is usually referred to as 3D printing because nothing like what we do has ever existed before. It’s easier to call it 3D printing because it is the most relatable reference point for consumers and businesses,” Kanik told 3DNatives in 2020.

“While there is indeed a three-dimensional print, what we do at Smart Cups is a unique microencapsulation process.”

The company made its debut with a line of energy drinks that require only the addition of water to transform the printed ingredients into a ready-to-drink beverage. These ingredients are enclosed within a plant-based shell that adheres to the bottom of the cup, which is made out of an eco-friendly bioplastic. When in contact with liquid, this shell activates, automatically stirring and instantly converting the cup into a beverage.

According to Kanik, Smart Cups hopes to expand its technology to other types of products including water purification, personal care and medication. Smart Cups’ partnerships include Mike Tyson’s cannabis company, The Ranch Companies and Compana Pet Brands.

“I feel like I have a responsibility to make a positive impact on the planet,” Kanik said. “The ability to provide micronutrients and water purification systems, in a sustainable and efficient manner, is the way that I can help the world.”

A recent study conducted by UCLA’s Institute of the Environment and Sustainability found that using Smart Cups with tap water reduced production energy consumption by 23 percent to 48 percent. This led to a significant 40 percent to 57 percent reduction in global warming potential, which measures the impact of production on atmospheric warming. Smart Cups funded, but was not involved, in the research.

Kanik was inspired to start Smart Cups on a “Taco Tuesday” night in 2011 when his drink was taking too long to arrive. Thirsty and impatient, he dreamt of an instant margarita. Teaming up with microencapsulation specialist Salvatore Celeste, he began to develop Smart Cups technology, using original manufacturing equipment and microencapsulation techniques.

“Maybe I was too stupid 11 years ago, and I didn’t realize how daunting of a task this was. There was no manufacturing equipment — we had to figure [Smart Cups technology] all out by ourselves,” Kanik said.

To continue reading this story, please visit www.cornellsun.com.

KANIK Continued from page 1

Gabriel Muñoz can be reached at gmunoz@cornellsun.com.

Marian Caballo can be reached at mcaballo@cornellsun.com.

Food star | Cornell alumnus Chris Kanik ’05 won $250,000 and the chance to work alongside Gordon Ramsay as the season one winner of “Gordon Ramsay’s Food Stars.”

COURTESY OF CHRIS KANIK ’05

Aunt Flow’s Kitchen Disrupts the Flow of Menstrual Stigma

BY DANIELA ROJAS Dining Editor & KATIE RUEFF Dining Contributor

Growing up with gut-twisting menstrual cramps, Armita Jamshidi ‘25 (majoring in Computer Science and College Scholar, fo cusing on the intersection between entrepreneurship and women’s health) knew one thing: she didn’t deserve to suffer through her pain. Uncomfortable with the possible long-term con sequences of traditional pain medication, Jamshidi instead relied on her grandma’s sooth ing Middle-Eastern recipes. Inspired by these recipes, she launched her small business in 2022 as She Balls. Now known as Aunt Flow’s Kitch en, her company is dedicat ed to helping menstruators mitigate period cramps with grandma-approved, science-backed “Cramp Bites.”

Coming to Cornell, Jam shidi was unable to replicate her comfort foods due to there being no Middle Eastern grocery stores in a local radius. As her cramps worsened, she ended up in the E.R. and struggled to get through daily life. Determined, she knew sitting through her pain would only feed its power. So, through the Women in Entrepreneurship Program, she coined the concept of “Cramp Bites.” Following positive and informative feedback, Jamshidi began to consider bringing the concept to life.

Cramp Bites, based on her grandma’s recipes, feature exquisite flavors, such as pistachio, sesame and rose. Each Cramp Bite package comes with a personalized letter, fueling you to feel capable of “chang[ing] the world, regardless of your menstrual agenda,” as she wrote

in our order’s letter. Encouraged even more by her company’s viral TikToks (@auntfloskitchen), we just had to give them a try.

When you first open a box of Cramp Bites, you are welcomed with an aro-

health experts, and ran a clinical trial for her product. After rigorous testing, the results were in: Cramp Bites are proven to reduce period cramp symptoms, sometimes within minutes of eating them! Although we weren’t tasting them

Speaking of nuts, Jamshidi has high hopes for the future of Aunt Flow’s Kitchen––including an allergy-friendly Cramp Bite! Planning to stick with the Middle-Eastern flavor diaspora, Jamshidi hopes to keep creativity at the forefront as she designs more products to alleviate other period problems (such as fatigue). Also considering partnering with period tracking apps like Clue and creating a kind of subscription model, Jamshidi has an endless flow of ideas to disrupt the stigma surrounding menstrual pain.

Daniela Rojas, dining editor, is a third-year student in the College of Arts & Sciences. She can be reached at dwise-rojas@ cornellsun.com.

Katie Ruef, dining contributor, is a frst year in the College of Arts & Sciences. She can be reached at kr468@cornell.edu.

sweetness (and just a touch of tang). With a warm smell, these vegan, gluten-free bites feel like a warm hug even before tasting them.

Each Cramp Bite features a crave-satisfying balance of textures and flavors, and a little extra kick to keep you looking forward to your next bite.

But it doesn’t just taste good! It’s science––and research-backed, too! Last year, through the Laidlaw Program, Jamshidi spoke with over 400 menstruators, consulted international

least confirm that these bites won’t rattle your digestive system! (Unless you have a nut allergy…)

Armita Jamshidi posing with her product, “Cramp Bites.”

The Corne¬ Daily Sun

Brenner Beard

Beard is a fourth year student in the College of Arts & Sciences. His fortnightly column Agree to Disagree is a collection of musings and opinions on campus and the Cornell community at large. He can be reached at brennerbeard@cornellsun.com

9/11 and the Obligation of Memory

Monday Sept. 11 marks the 22nd anniversary of the brutal terrorist attacks of 9/11. 22 years is about as old as I am, and years beyond the newest Cornellians in the class of 2027. Yet, despite the march of time, the annual ritual begins anew every September 11th. The social media posts go-up, and come September 12th, we move on with our lives.

Over the course of my lifetime, this ritualized act of remembrance has increasingly become more confined to “feeds” of the various online spaces we inhabit. This year, our memory of 9/11 ran the gambit of Instagram graphics emblazoned with various hashtag equivalents of “Lest We Forget” to students cracking insensitive jokes of “happy 9/11.” Regardless of perverse social media style, there is the commonality of our persistence in remembrance. At the same time, however, why remember at all if memory itself consists of hollow hashtags and “memes.”’ As the wars in Iraq and Afghanistan born of that September morning 22 years ago come to the close, and generations of students enter adulthood increasingly ignorant of 9/11’s consequences, we find our institutions clinging to a faded national memory while it seems that my generation desperately tries to move on. Somewhere along the line and caught between these conflicting perspectives, our memory of 9/11’s true significance became a victim.

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Despite what the clock that pushes each of us closer to graduation may say, time as it pertains to history is not linear. As is the case with 9/11, events of the past become etched in our memory and recur with disregard for the shackles of time. Just a few years ago, Cornell unveiled a memorial to 21 of our University’s alumni who perished in the towers in 2001. Looking at that marble plaque last year, I was struck by the permanence with which each of those names exists, the strength of the voices with which they call out to you

also

here in the present. The names of those 21 Cornellians and their graduation years reach through the years and very quickly dispel any notion that 9/11 exists in the past.

Far from linear, the past and its memory is also living, forever shaping those who live with it. I spoke the other day with a local about the upcoming anniversary. He told me a story of a dear friend of his who died that day: Unlike the planes destined for the towers and the Pentagon,

his friend was on flight 93 and heroically helped to take down the hijackers, preventing further deaths in the process. What struck me the most about his story, however, was that this man could, down to the letter, remember the last words of the phone call the friend made to his family from the doomed plane. 22 years after the tragedy and those words speak to him as if his friend was alive and saying them into his own ear now. For so many, 9/11 doesn't start on Sept. 11 and end Sept. 12, its memory walks beside them everyday.

To truly engage in remembrance we must step away from our rituals and screens and recognize the potency of memory. History is a discombobulated mess that no amount of time can prevent from rearing its head in the present. The thousands of Americans tragically killed on Sept. 11th, 2001, the hundreds of thousands of civilians killed in Afghanistan, the further thousands of disabled American service-members, and the hundreds of first responders suffering through the medical conditions caused by 9/11, are all vignettes which showcase how this one day in 2001 defined and continues to define our country in the modern era. In recognizing the effects of 9/11, we must also recognize that remembrance cannot be left up to social media accounts or simply honoring the fallen. In order to truly be responsive to those voices which call to us from the past, we must be attentive to the obligation that comes with memory.

In memorializing 9/11, we are also accepting responsibility. As it should be with all history, remembering 9/11 is about overcoming our present ignorance while also critically analyzing our past to inform the future.

Contemporarily, our jokes, politics and social media-like tendencies toward 9/11 diminish its significance as an overly patriotic “remember the alamo” type battle-cry and distort the humanity of the anniversary. Rather than engaging in this style of pseudo-remembrance, we must instead engage with the voices of those who lost their lives. Tell their stories and retell their stories. Rather than posting a thumbnail image on your feed, we must instead support platforms in which individual sacrifice can be discussed and honored. Humanity is far more important than consumer-ized nationalism and corporate virtue-signaling.

Like it or not, the past is always alive and well in the present. 9/11/2001 is a day whose tragedies can be felt just as strongly today, 22 years later. You may not see the costs as clearly in the present, but we get to choose whether or not we’re ignorant of them. Despite our impulse to post and hashtag, remembrance can’t be done half-heartedly or with the touch of a button. To truly do memory justice, we must be stewards of the past, mindful in the present and constantly preparing for a better future.

Brenner

"Far from linear, the past and its memory is

living"

Mr. Gnu

Mr. Gnu

Mr. Gnu

SC I ENCE

Weill Develops Gene Editing Tool for Cancer Mutations

By KAITLYN LEE Sun Staff Writer

Prof. Lukas Dow, biochemistry, and his team published a study in Nature on Aug. 16, detailing a new, more specific gene editing tool that they created to study cancer mutations through preclinical mice models.

Dow began his research working with CRISPR-Cas9, another gene editing tool that targets specific DNA regions to mimic and study similar mutations seen in patient tumors.

“We actually know very little about how those specific mutations cause tumor growth and lead to therapy resistance or response,” Dow said. “So we have had a large, coordinated effort to try and understand those mutations that occur across many patients’ tumors.”

To accomplish his goal, Dow moved to optimizing base editing enzymes and developing a system that allows him to turn the expression of these enzymes on and off with doxycycline, an antibiotic also typically used to regulate gene expression. Dow used these enzymes to then create mutations in cells of animal mod -

els and compare them to cells without tumor mutations.

The gene editing tool utilizes technology from CRISPRCas9, according to Dow. The team combined Cas9, an enzyme that cuts DNA, and guide RNA, a type of RNA that determines which DNA region Cas9 cuts, with apolipoprotein B mRNA editing enzyme, catalytic polypeptide — an enzyme commonly known as APOBEC that creates single base mutations in DNA.

Dow explained that the guide RNA takes Cas9 to a specific region in the genome, allowing Cas9 to then cut one of the DNA strands at the targeted site. Afterwards, APOBEC changes the nucleotide bases in the DNA, typically changing cytosines to uracils or thymines. Additionally, the gene editing tool has a domain called the uracil glycosylase inhibitor, which prevents the newly changed bases from being reverted back to cytosine.

However, Dow and his team encountered some challenges during the process. For example, frequent expression of APOBEC resulted in unwanted and random mutations of var -

ious RNA molecules in cells. These essential RNAs could potentially become translated into dysfunctional proteins that are detrimental for the cell.

To address this, a single gene copy that produces APOBEC is integrated into the cell’s genome and controlled by gene expression regulator doxycycline in order to determine how much APOBEC is produced.

In addition, the gene expression of APOBEC varies among different types of cells. Not all cells in the intestine, liver and pancreas produced this enzyme when incorporated into their genome. Thus, Dow inserted two copies of the gene in these cells instead of one to compensate for the lower expression of APOBEC.

Dow also encountered difficulties delivering components of the gene editing tool, or doxycycline, into certain tissues such as the brain. Dow proposed that various other delivery methods could be used in lieu of the gene editing tool, such as using viruses or zapping cells to open up the cell membrane. On the contrary, doxycycline could be directly

injected to the brain in order to activate the gene editing tool.

Despite these difficulties, the gene editing tool presents favorable opportunities to understand the effects of single-base genetic changes on tumors through models and determine which therapy is effective against cancer. It could also be used as treatment itself by editing and reverting genetic changes observed in tumors. The tool could even be used to study other disorders outside of cancer.

“There are ways that the gene editing tool can be used as both therapy, as well as development of models to understand disease,” Dow said. “If you’re doing it in a clinical setting, there are a range of different editing enzymes that allow you to create different types of mutations.”

To continue reading this article, please visit www.cornellsun.com.

Landau Lab Studies New Technique for RNA Splicing

By KAITLIN CHUNG Sun Staff Writer

Researchers in the Landau lab, led by Dr. Dan Landau, hematology and medical oncology, recently developed a new technique to investigate how mutations in RNA splicing can lead to clonal hematopoiesis and myelodysplastic syndrome — a topic with greater implications regarding the pathophysiology of cancer.

Clonal hematopoiesis is a symptomless condition with mutated blood cells that acts as a precursor to the rarer type of blood cancer, myelodysplastic syndrome, where patients have low levels of functional blood cells.

RNA splicing refers to the cutting up and reassembling of genetic

transcripts in cells. It is a naturally occurring process required to prepare genetic transcripts for use by cells and can lead to the formation of distinct proteins with different functions.

Prior work with bulk sequencing, an approach that enables researchers to study transcriptomes across cell populations, revealed that many cancers possess mutations in RNA splice factors, proteins that regulate the splicing process. They found that the most prevalent mutation in MDS is in SF3B1, an essential splice factor. The mutation causes abnormal splicing and ultimately produces nonviable protein products. However, bulk sequencing has two major limitations.

“In clonal hematopoiesis and

MDS, the bone marrow has both normal cells and mutated cells. With bulk sequencing, it’s difficult to know whether the change is in normal or mutated cells,” Landau said.

The other challenge is that there isn’t just one cell type but instead a whole range of cell types, and because bulk sequencing averages across these cell types, researchers can have difficulty telling which cells the aberrant splicing is coming from.

To address these limitations, the Landau lab developed genotyping of transcriptomes, a single-cell method, in 2019. GoT allowed them to simultaneously examine a cell’s genetic sequence and determine the presence of the SF3B1 mutation.

In the current study, the researchers expanded GoT to profile gene mutations and gene expression patterns in cells and to map splicing changes in mutant cells compared to the normal cells. The researchers also integrated a separate method for detecting protein surface markers on individual cells. Their new technique, called GoT-Splice, enables greater precision in characterizing abnormal splicing events and how they arise in cell development processes.

“We wanted to capture the variation across cell types and compare mutant and normal cells to see differences at the splicing and RNA regulatory levels,” said Dr. Mariela Cortés-López, a postdoctoral researcher in the Landau lab postdoc. “We wanted to see what could explain the phenotypes we observed in these diseases, how the mutations

are connected to physical effects on patients.”

One of the mutations identified in MDS was in a protein called BAX, which is a critical regulator of programmed cancer cell death. With the splicing abnormality, BAX resisted cell death instead of causing it, suggesting on a clinical level that patients with a mutation for BAX will be less responsive to specific drug treatments.

The researchers performed the same experiments with clonal hematopoiesis in which a mutated blood cell clones itself to create a population of identical cells. They found that even in early stage clonal hematopoiesis, splicing mutations in MDS — including in BAX — are already present, even though the condition is benign. The trajectory for this line of work is to better understand the cloning process and characterize the effects of the mutations in the absence of visible disease.

The Landau lab will continue to explore the applications of GoTSplice to examine splice factor mutations in cancer and understand its effects in patients.

“As a physician-scientist, I have the patients in my mind,” Landau said. “It’s important for me to think about the translational implications of our research and how to get the knowledge back into the clinic. We want to make fundamental discoveries about how the body works, and we also want them to have an impact on our patients.”

Kaitlin Chung can be reached at khc73@cornell.edu

Medical oncology | The Landau lab’s work with RNA splicing has improved their understanding of the pathophysiology of cancer.

Kaitlyn Lee can be reached at klee@cornellsun.com

CRISPR-Cas9 | Gene editing tools target specific DNA regions to mimic and study similar mutations seen in patient tumors.