제 255회 NEBS Monthly meeting 개최를 다음과 같이 알려드립니다.
일시: 2017년 6월 29일 (목요일) 오후 6시 30분
(7시 이후 엘레베이터 이용이 제한되니 가급적 7시 이전에 오시길 부탁드리며, 7시 이후의 경우 Security guard에게 미팅 참석 여부를 확인 후 엘리베이터 이용을 부탁해 주세요.)
New Research Building, 10th floor conference room
77 Ave Louis Pasteur, Boston, MA 02115
6:20 - 7:00 저녁식사
7:00 - 7:10 공지사항
7:10 – 7:55 Presentation 1 -
“Multidimensional tracking of GPCR signaling via peroxidase-catalyzed proximity labeling"
By Jae Ho Paek, Ph.D. Candidate (Chemical Biology, Harvard University)
7:55 - 8:40 Presentation 2 –
“SIRT2 as metabolic regulator in human induced pluripotency”
By Young Cha, Ph.D. (McLean Hospital, Harvard Medical School)
9:00 - 11:00 뒷풀이 (Longwood Grill)
발표 관련 abstract는 아래를 참조 바랍니다.
Multidimensional tracking of GPCR signaling via peroxidase-catalyzed proximity labeling
G-protein-coupled receptors (GPCRs) play critical roles in regulating physiological processes ranging from neurotransmission to cardiovascular function. Current methods for tracking GPCR signaling suffer from low throughput, modification or overexpression of effector proteins, and low temporal resolution. To address these issues, we show that peroxidase-catalyzed proximity labeling can be combined with isobaric labeling and quantitative mass spectrometry to enable quantitative, time-resolved measurement of GPCR agonist response in living cells. Using this technique, termed “GPCR-APEX,” we track activation and internalization of the angiotensin II type 1 receptor and the β2 adrenoceptor. These receptors co-localize with a variety of G proteins even before receptor activation, and activated receptors are largely sequestered from G proteins upon internalization. Additionally, the two receptors show differing internalization kinetics, and we identify the membrane protein LMBRD2 as a potential regulator of β2 adrenoceptor signaling.
SIRT2 as metabolic regulator in human induced pluripotency
A hallmark of cancer cells is the metabolic switch from oxidative phosphorylation (OXPHOS) to glycolysis, a phenomenon referred to as the “Warburg effect”, which is also observed in primed human pluripotent stem cells (hPSCs). Here, we report that downregulation of SIRT2 and upregulation of SIRT1 is a molecular signature of primed hPSCs and that SIRT2 critically regulates metabolic reprogramming during induced pluripotency by targeting glycolytic enzymes including aldolase, glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase, and enolase. Remarkably, knockdown of SIRT2 in human fibroblasts resulted in significantly decreased OXPHOS and increased glycolysis. In addition, we found that miR-200c-5p specifically targets SIRT2, downregulating its expression. Furthermore, SIRT2 overexpression in hPSCs significantly affected energy metabolism, altering stem cell functions such as pluripotent differentiation properties. Taken together, our results identify the miR-200c-SIRT2 axis as a key regulator of metabolic reprogramming (Warburg-like effect), via regulation of glycolytic enzymes, during human induced pluripotency and pluripotent stem cell function.