Revealing the root causes of colon cancer: Three questions for Dr. Ali Lanctot Chomiak
September 13, 2018
Although the overall prevalence of colon cancer has steadily dropped since the 1980s, a close look at the data from recent years reveals a disturbing trend — despite the broader decrease, colon cancer cases are climbing at an alarming rate in younger people.
Regular screening for the disease usually begins at age 50, which helps doctors catch cancers before they take hold and spread. Since people younger than 50 typically do not undergo annual screening, colon cancers may not be caught until much later, making treatment much more difficult.
Although scientists know a lot about the factors that cause cancer, there are some important gaps in knowledge that, once revealed, could lead to the development of new, improved therapies.
Dr. Ali Lanctot Chomiak, a postdoctoral fellow here in the lab of Dr. Scott Rothbart, is working to get to the root of this problem by studying the molecular changes that give rise to colon cancer. To do so, she’s focusing on an epigenetic process called DNA methylation, an ensemble of small tags on DNA that tell our genes when they should be expressed and to what extent.
To understand methylation, it’s helpful to think about what you’re doing right now — reading.
We read by recognizing certain patterns and groups of letters (aka words) on a page and assigning them meaning. In much the same way, certain methylation patterns on our DNA help the body read and identify when the instructions in a certain gene should be acted upon and when they should not. In many diseases, including cancer, these patterns get scrambled, causing certain genes to become active or inactive at the wrong time. In cancer, this could mean a gene responsible for promoting cell division doesn’t get turned off when it should, allowing too many cells to grow and invade other tissues.
To support her work, the National Cancer Institute recently awarded Lanctot Chomiak a Ruth L. Kirschstein National Research Service Award, a prestigious grant developed to support the training of the country’s most talented pre- and postdoctoral scientists. We caught up with her to talk about her research and how support from federal funding propels innovative scientific inquiry.
Q: Tell us about your research. What will this award support?
ALC: We know that DNA methylation patterns often are irregular in cancer; this is particularly true in colon cancer. At the same time, existing medications that target methylation to treat cancer are not always effective or they have side effects. I want to figure out how and why these methylation patterns change and how they give rise to malignant cells, with the goal of developing improved treatments.
Specifically, I study a protein called UHRF1, which helps maintain methylation patterns on the DNA. UHRF1 also is overly abundant in cancers and, again, even more so in colon cancers. I’m investigating how and why UHRF1 is overexpressed and trying to figure out if targeting and reducing levels of UHRF1 may be an effective way to fight cancer.
I’m really excited about this project. It’s a great opportunity to uncover new insights into the molecular drivers of colon cancer and has the potential to inform the development of new epigenetic cancer treatments.
Q: You’re using some pretty cool techniques in the lab. Can you fill us in?
ALC: For my experiments, I am modeling colon cancer with intestinal organoids, which are an exciting new technology that helps us study organ development and cancer. These organoids, or “mini-guts,” are kind of like bonsai trees — they have many of the same features as a real, full-size intestine but are about the diameter of a human hair.
They’re a great model because they are relatively easy to manipulate and they mimic gut structure and organization more closely than traditional cancer cell lines used in the lab. For example, we can grow normal organoids from cells taken from a healthy intestine or we can grow cancerous organoids by using samples from tumors or polyps. We can also cause cells in our healthy organoids to turn cancerous, modeling in the lab what happens inside the body.
Q: How does this grant help your work?
ALC: Funding from the National Cancer Institute provides me with critical support at a key time during my development as an independent scientist.
On a personal level, this award gives me confidence knowing that the excitement I have for my ideas is shared among my peers. A lot of careful literature review and focused project design goes into writing and getting a grant, and the peer-review process helps validate my study goals and plan. The simple fact that it was funded means other scientists believe both the project and me are worth supporting and that the study is a valuable use of resources and time. It’s very gratifying.
Research reported in this post was supported by the National Cancer Institute of the National Institutes of Health under award number 1F32CA225043-01A1. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Ali Lanthi Chomiak, Mtaalamu wa Ugonjwa wa Ugonjwa wa Ugonjwa wa Ugonjwa wa Ugonjwa wa Ugonjwa wa Ugonjwa wa Ugonjwa wa Ugonjwa wa Ugonjwa wa Ugonjwa wa Ugonjwa wa Ugonjwa wa Ugonjwa wa Ugonjwa wa Ugonjwa wa Ugonjwa wa Ugonjwa wa Ugonjwa wa Ugonjwa wa Ugonjwa wa Ugonjwa wa Ugonjwa wa Ugonjwa wa Ugonjwa wa Ugonjwa wa Ugonjwa wa Ugonjwa Uchunguzi wa kawaida wa saratani huanza katika umri wa miaka 50 na husaidia waganga kugundua saratani kabla ya kuenea. Kwa kuwa watu walio chini ya miaka 50 kwa kawaida hawafanyi uchunguzi wa kila mwaka, saratani ya utumbo inaweza kugundua hadi baadaye, na kufanya matibabu kuwa magumu zaidi. Ingawa wanasayansi wanajua mengi kuhusu sababu zinazosababisha kansa, kuna mapungufu muhimu katika maarifa ambayo, mara tu yatakapofunuliwa, yanaweza kuongoza kwenye maendeleo ya matibabu mapya na bora. Ali Lanthi-Chomyak, mwanachama wa utafiti wa postdoctoral hapa katika maabara ya Dk Scott Rothbart, anafanya kazi ya kupata mizizi ya tatizo hili kwa kujifunza mabadiliko ya molekuli ambayo husababisha kansa ya utumbo. Kwa kufanya hivyo, yeye ni kuzingatia mchakato epigenetic aitwaye DNA methylation, seti ya vitambulisho vidogo juu ya DNA kwamba kuwaambia jeni zetu wakati wao lazima kuonyeshwa na kwa kiasi gani. Kuelewa methylation, ni muhimu kufikiri kuhusu nini wewe ni kufanya sasa hivi <unk> kusoma. Tunasoma kwa kutambua mifumo fulani na vikundi vya herufi (maana yake maneno) kwenye ukurasa na kuwapa maana. Kwa njia hiyohiyo, mifumo fulani ya methylation kwenye DNA yetu husaidia mwili kusoma na kutambua wakati maagizo katika jeni fulani yanapaswa kutekelezwa na wakati hawapaswi. Katika magonjwa mengi, ikiwa ni pamoja na kansa, mifumo hii huchanganyikiwa, ikisababisha jeni fulani kuwa hai au zisizo na kazi wakati usiofaa. Katika kansa, hii inaweza kumaanisha jeni linalohusika katika kukuza mgawanyiko wa seli haizuiwi wakati inapaswa, ikiruhusu seli nyingi sana kukua na kuvamia tishu nyingine. "Kwa msaada wa kazi yake, Taasisi ya Kitaifa ya Saratani hivi karibuni ilimpa Lancton Chomiak tuzo ya ""Ruth L. Kirschstein National Research Service Award,"" ruzuku ya kifahari iliyoundwa kusaidia mafunzo ya wanasayansi wa kitaaluma wa nchi." Tulimfikia ili tuzungumze juu ya utafiti wake na jinsi msaada kutoka kwa ufadhili wa shirikisho unavyoendesha uchunguzi wa kisayansi wa ubunifu. Q: Tuambie kuhusu utafiti wako. Tuzo hii itasaidia nini? "Kama ilivyoelezwa hapo juu, ""mfano wa methylation ya DNA ni mara nyingi isiyo ya kawaida katika saratani, hasa katika saratani ya utumbo.""" Dawa zilizopo ambazo zinatumia methylation kwa kansa hazifanyi kazi au zina athari mbaya. "Kama ni lazima, ni muhimu kujua jinsi na kwa nini mifumo hii ya methylation inabadilika na jinsi inavyozalisha seli mbaya, na lengo la kuendeleza matibabu bora. """ Kwa mfano, kuna protini inayoitwa UHRF1 ambayo husaidia kudumisha muundo wa methylation kwenye DNA. UHF-1 pia ni ya wingi sana katika saratani na, tena, hata zaidi katika saratani ya utumbo. """Ninachunguza jinsi na kwa nini UHRF1 inaonyeshwa kupita kiasi na kujaribu kujua ikiwa kulenga na kupunguza viwango vya UHRF1 inaweza kuwa njia bora ya kupambana na saratani." Mimi ni kweli msisimko kuhusu mradi huu. Ni fursa kubwa ya kufunua ufahamu mpya katika madereva ya molekuli ya kansa ya utumbo na ina uwezo wa kuarifu maendeleo ya matibabu mapya ya saratani ya epigenetic. Q: Wewe ni kutumia baadhi ya mbinu pretty baridi katika maabara. Je, unaweza kutueleza? "Kupitia utafiti wa ""Celtic,"" tumeweza kugundua kwamba saratani ya utumbo wa tumbo la uzazi ni moja ya njia za kuendeleza maendeleo ya viungo vya mwili na kansa." Vipande hivi vya mwili vinafanana na miti ya bonsai, lakini vina vipimo sawa na tumbo la binadamu. Wao ni mfano mkubwa kwa sababu wao ni rahisi kudhibiti na wao kuiga utando na shirika karibu zaidi kuliko jadi ya saratani seli mistari kutumika katika maabara. Kwa mfano, tunaweza kukuza organoids ya kawaida kutoka kwa seli zilizochukuliwa kutoka kwa matumbo yenye afya au tunaweza kukuza organoids ya kansa kwa kutumia sampuli kutoka kwa uvimbe au polyps. Pia, tunaweza kugeuza chembe za mwili wetu kuwa kansa kwa kutumia mifano ya maabara. Q: Je, mpango huu wa misaada unasaidiaje? """Msaada wa kifedha kutoka kwa Taasisi ya Kitaifa ya Saratani unanipa msaada muhimu wakati muhimu wakati wa maendeleo yangu kama mwanasayansi huru." Katika kiwango cha kibinafsi, tuzo hii inanipa ujasiri kujua kwamba msisimko ninao kwa mawazo yangu unashirikiwa kati ya wenzangu. """Mchoro wa maandishi na muundo wa mradi unaelekezwa kwa uangalifu unahusika katika kuandika na kupata ruzuku, na mchakato wa ukaguzi wa wenzao unasaidia kuthibitisha malengo yangu ya utafiti na mpango." "Kwenye ukweli kwamba ilifadhiliwa, wanasayansi wengine wanaamini kwamba mradi huo na mimi tunastahili kuungwa mkono na kwamba utafiti huo ni matumizi ya thamani ya rasilimali na wakati.""" Ni jambo lenye kuridhisha sana. Utafiti ulioelezwa katika chapisho hili uliungwa mkono na Taasisi ya Kitaifa ya Saratani ya Taasisi ya Kitaifa ya Afya chini ya nambari ya tuzo 1F323C25043-01A1. Maudhui ni wajibu pekee wa waandishi na si lazima kuwakilisha maoni rasmi ya Taasisi za Taifa za Afya.