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Masks Strongly Recommended but Not Required in Maryland, Starting Immediately

由于马里兰州呼吸道病毒呈下降趋势, masking is no longer required but remains strongly recommended in 约翰霍普金斯医学院 clinical locations in Maryland. Read more.

Research

拉斯克奖得主格雷格·塞门扎，m.s.D., Ph.D.

C. 迈克尔·阿姆斯特朗基因医学教授, Pediatrics, Medicine, Oncology, 放射肿瘤学, 生物化学

格雷格西门Dr. 格雷格西门

Gregg L. Semenza, M.D., Ph.D. of the Johns Hopkins University 医学院 was awarded the 2016 Albert Lasker Basic Medical Research Award by the Albert and Mary Lasker Foundation. 塞门扎和共同获奖的威廉·G. Kaelin, Jr., M.D. 丹娜-法伯癌症研究所的Peter J. 牛津大学的拉特克利夫说, were recognized for their “discovery of essential pathways by which human and animal cells sense and adapt to the presence of oxygen.”

In 1992, Semenza and co-authors announced their ground-breaking discovery of hypoxia inducible factor 1 or HIF-1, 是什么帮助细胞应对低氧水平. The discovery has far-reaching implications in for understanding low oxygen health conditions like coronary artery disease and tumor growth. Since then Semenza has identified genes turned on by HIF-1 that control energy production, 红细胞的生成和血管的生长. 他目前正在研究HIF-1在癌症中的作用, 缺血和慢性肺病, 是美国最常见的死亡原因.S. population.

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发现的时间轴

1991年:缺氧开启了一个基因

格雷格·塞门扎，医学博士，博士.D., 和Stylianos Antonarakis, MDDCh, identified two enhancers - DNA sequences near genes that bind proteins to help control the gene - that work specifically when oxygen is low. The other enhancers were found on either side of the gene for erythropoietin, 一种激素，它发出信号，使更多的红细胞产生. Once enhancer turns the gene on in the kidneys and the other in the liver.

1991年，缺氧开启一种基因，幻灯片1

1992年:HIF-1与DNA结合

缺氧是身体细胞缺氧的一种状态. 格雷格西门，医学博士，黄光博士.D., aptly named the protein that binds the enhancers of the erythropoietin gene in response to low oxygen hypoxia inducible factor 1 (HIF-1).

1992年，HIF1与DNA结合

1993年:HIF-1对缺氧有反应

HIF-1 protein levels increased when oxygen levels were reduced in all mammalian cell lines tested, suggesting that turning up HIF-1 levels may be a universal response to hypoxia.

1993年HIF1对缺氧的反应特写幻灯片3

1996年:HIF-1激活VEGF

Semenza实验室发现HIF-1可以激活VEGF基因, 是什么控制着血管化——新血管的产生. 血管化对伤口愈合很重要, but it is also required for tumors to grow and spread throughout the body.

1996年，HIF1激活VEGF

1997年:HIF-1可能与癌症有关

HIF-1 is found to turn on an oncogene—a gene that when dysregulated leads to development of cancer. This provides the first evidence that cancer cells need HIF-1 to adapt to low oxygen environments.

1997年，HIF1可能与癌症有关

1998年:我们不能没有HIF-1

The Semenza lab shows that HIF-1 is essential for survival of mouse embryos. 没有HIF-1，心脏、血管和血液就不会发育.

1998年，我们不能没有HIF1

1999年:HIF-1水平在许多癌症中都很高

HIF-1在许多人类癌症中被发现高表达. This suggests that inhibiting HIF-1 may be a potential therapeutic for the treatment of cancer.

1999年，HIF1水平在许多癌症中都很高

2000年:HIF-1可以预防中风

Turning on extra HIF-1 with chemicals reduces the amount of damaged tissue in the brains of mice that have had strokes. This suggests therapeutics may be developed that can reduce the damage left by strokes.

2000 HIF1保护中风

2003年:HIF-1在小鼠体内生成新血管

Injecting a virus engineered to make HIF-1 causes blood vessels to grow in mice. This suggests that increasing HIF-1 levels may be useful in patients with coronary artery disease or leg circulation problems.

2003年，HIF1在小鼠中制造新血管

2005: HIF-1对心脏病起保护作用

Hopkins researchers report that inherited differences in the gene for HIF-1 influence the body’s response to coronary artery disease.

2005 HIF1 plays a protective role against heart disease Featured Slide 10

2008/2009:抗癌药物通过阻断HIF-1发挥作用

塞门扎的团队发现了这两种药物, 地高辛和吖啶黄, block HIF-1 from making VEGF and other proteins that are necessary for tumor growth in animal models. Both drugs have been used in the past for other purposes and can now be tested in cancer patients.

抗癌药物通过阻断HIF1发挥作用特写幻灯片11

2009年:HIF-1可用于治疗血液循环不良的患者

如果血液供应受限，就会造成组织损伤. 衰老和糖尿病的后果之一是血液循环不良. 塞门扎的研究小组用HIF-1基因疗法治疗糖尿病小鼠, which helped improve blood flow to their limbs and prevented tissue damage. In a separate experiment they combined HIF-1 gene therapy with blood stem cells to improve circulation in very old mice and prevent limb loss.

2009 HIF1 may be used to treat patients with poor circulation Featured Slide 12

2014年:HIF可能是治疗耐药癌症的关键

Semenza’s team found that a common chemotherapy drug caused triple-negative breast cancer cells to thrive by dialing up levels of HIF. The good news was that treating mice with a combination of a HIF inhibitor and chemotherapy shrank their triple-negative tumors by 30 percent more than treatment with paclitaxel alone.

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2014年HIF可能是治疗耐药癌症的关键

对癌症的影响

肿瘤面临着一个核心问题:随着它们越来越大, cells near the middle are increasingly cut off from the body’s oxygen supply. 因为HIF能感知氧气水平, it’s critical to stimulating the growth of new vessels to supply the tumor. Semenza and others are working to find and test therapeutics that would block HIF, 这可能是某些肿瘤盔甲上的致命漏洞. 

对糖尿病的影响

相对于没有患病的人, patients with type 2 diabetes face a high risk of losing a limb to amputation due to poor circulation. Semenza’s work suggests HIF-1 could be the key to restoring circulation before it’s too late. By treating diabetic mice with a virus engineered to increase HIF-1 production, 他的团队能够增加他们四肢的血流量.

What's Next?

Researchers are at work on potential therapies that would change HIF-1 activity to treat conditions such as cancer, 糖尿病和中风. For example, a drug known as GSK1278863 is being clinically tested as a treatment for patients with anemia associated with chronic kidney disease. 该药抑制HIF以维持血红蛋白水平.

Dr. 塞门扎关于HIF-1的发现

格雷格·塞门扎，m.s.D., Ph.D. 谈到了他在20世纪90年代对蛋白质HIF-1的开创性发现, 它在治疗贫血和癌症方面的潜在应用, 以及作为研究人员的生活.

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科学发现的乐趣

格雷格·塞门扎，m.s.D., Ph.D., of the Johns Hopkins McKusick-Nathans Institute of Genetic Medicine on the excitement and unpredictability of being a scientist.

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#明日发现:耐化疗乳腺癌干细胞

而化疗攻击并杀死99%的乳腺癌细胞, 它留下了耐化疗的癌症干细胞, 哪些会导致转移性肿瘤. Dr. 格雷格西门’s team has identified a way to overcome the resistance of cancer stem cells to chemotherapy, 完全根除小鼠乳腺肿瘤.

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  • 格雷格·塞门扎实验室

    The 格雷格·塞门扎实验室 studies the molecular mechanisms of oxygen homeostasis. 我们克隆并鉴定了缺氧诱导因子1 (HIF-1)。, 一个基本的螺旋-环-螺旋转录因子.

    Current research investigates the role of HIF-1 in the pathophysiology of cancer, 脑缺血和心肌缺血, 慢性肺病, 哪些是美国最常见的死亡原因.S.

    研究领域: cancer, oxygen, 肺部疾病, genomics, HIF-1, 发病机理, 心肌缺血

    格雷格·塞门扎，m.s.D., Ph.D.

    首席研究员

    格雷格·塞门扎，m.s.D., Ph.D.

    Department

    Pediatrics