I do like Dr. Philip Larsen's guideline for me-

"Let your compound-treated animal reached the steady state (multiple-dose is necessary), then you can do anything you want. Everything can show the improvement about metabolic syndrome is OK. Try to let the compound mechanism story can mimic the natural physiological mechanisms, that's will be better."


Maybe he gave me this simple rule because I'm a rookie. But this makes the drug discovery project become easier!!

I'm grateful there has Dr. Philip Larsen at that conference. He is a genius, definitely!!!!!!
I like and respect Dr. Philip Larsen very much. I do like him and Eli Lilly!!!!!!


Increase in physical activity energy expenditure is associated with reduced metabolic risk independent of change in fatness and fitness. Diabetes Care. 2007 Aug;30(8):2101-6.
→ This paper makes me miss you so much..

Endocannabinoids, FOXO and the metabolic syndrome: Redox, function and tipping point - The view from two systems. Immunobiology. 2009 May 18. [Epub ahead of print]
→ I do believe you'll like this paper!!!!!! From FASEB SRC to EB2010, I'm really very happy I graw up in FASEB and APS. Good luck for your grant writing, you are the best!!!!!!

Role of lipid-derived mediators in skeletal muscle insulin resistance. Am J Physiol Endocrinol Metab. 2009 Jul 14. [Epub ahead of print]

Therapeutic regulation of apoB100 metabolism in insulin resistance in vivo. Pharmacol Ther. 2009 Sep;123(3):281-91. Epub 2009 May 31.

Got an oversea invitation card from EB2010..
I believe this time will be much more easier in US immigration.




I really really want to see this in vivo data..


Adipose tissue-skeletal muscle crosstalk: Are endocannabinoids an unwanted caller? Diabetologia (2009) 52:571–573 (Fig.1)

Cannabinoid type 1 receptors in human skeletal muscle cells participate in the negative crosstalk between fat and muscle. Diabetologia (2009) 52:664-674

Ahhhhh~ So happy could see this.

Orlistat accelerates gastric emptying and attenuates GIP release in healthy subjects. Am J Physiol Gastrointest Liver Physiol. 2009 Mar;296(3):G482-9.

The role of endocannabinoids in the regulation of gastric emptying: alterations in mice fed a high-fat diet. Br J Pharmacol. 2008 Mar;153(6):1272-80.


Congrat to Eric, let's try together!!!!!!

Eric → Dr. Andreas Zimmer. From both of them, I do believe I'm a super lucky RA.
I do believe finally there has one day I can shake hand with Dr. Vincenzo Di Marzo!!!!!!

Starting to consider (USA) PhD application for Fall 2011-

GRE Analytical Writing: 9/21/2009–5/7/2010;
GRE Verbal Reasoning & Quantitative Reasoning: 6/12/2010 or Oct 2010.


Change cell phone nomber, e-mail address, web account;
Delete, format the three years I spent in here.


‧ Achieving the impossible, trust is everything and never betray partner's trust.
‧ Great leaders are brave and honest.
That's Mark taught vivi at the past two years.

"The Experimental Biology 2010 abstract submission deadline has been extended to Monday, November 9 at 5:00PM EST."

→ No mater finally I can submit abstract or not, I'll go to EB2010. My new project leader he says vivi you "should" attend this and keep touch with those kindly forieng friends/teachers. That's really important. I look forward to meeting APS/NIDDK and ASPET in Apr 2010..


"The primary goal of the FASEB MARC Program is to encourage underrepresented minorities to enter careers in research in the biomedical sciences. The program will focus on increasing participation by African Americans, Hispanics, Latinos and Native Americans, but the Program is not limited to those four groups and provisions are made to include others as appropriate.

→ Some other PhD students ask me about how to get the travel award, because they say that's really difficult for Asia student. I really appliciate for your kindness and help thus I bacame the first one who got FASEB MARC Travel Award, in Taiwan. That's really important and meaningful to Taiwanese- Make us believe that United States is really an open country.


"Adipose Tissue Biology (J3)
Organizers: Sheila Collins, Karsten Kristiansen and Silvia Corvera
January 24 - 29, 2010 • Keystone Resort • Keystone, Colorado

Following Session is for Neuronal Control of Appetite (J4)
8:00 - 11:00 AM Thinking Outside of the Hypothalamus
Marta Korbonits, Barts and The London, Queen Mary's School of Medicine and Dentistry, UK
Cross-Talk of Endocannabinoids and Ghrelin"

→ So happy could see ECS become a topic in a symposia directed by NIH/NIDDK..


"Metabolism and Cancer Progression (X4)
Organizers: Eileen P. White, Craig B. Thompson and Chi Van Dang
March 12 - 17, 2010 • Fairmont Hotel Vancouver • Vancouver, British Columbia"

→ So happy to see this. You should know this!!!!!!
Take a look the meeting program, you'll find spleen tyrosine kinase (Syk) still is a good chance.. (← that's why I do like drug discovery.. )


"Triglycerides and Triglyceride-Rich Particles in Health and Disease (A3)Organizers: Robert H. Eckel, Ira J. Goldberg and Ruth McPherson
January 9 - 14, 2010 • Big Sky Resort • Big Sky, Montana"

→ I just tell this to Dr. Eric Yen, tell him they met each other at FASEB conference. They should meet again because Eric really want to see some human data..

I really like my new project leader.
He is almost the same as you- everything can be talked!!!!!!


Show you things I have learned from these days prepare for attending EB2010..

1) Mice may not be a good model for human diabetes, that's why data from DIO rats become much more important now!!
Man or Mouse – It's Important in Diabetes Research

2) In skeletal muscle cells from individuals with early-onset diabetes, the gene for PGC-1α is hypermethylated and shows reduced expression levels. DNA methylation occurs rapidly when cells from healthy individuals are exposed to factors linked to diabetes such as the fatty acid, palmitic acid, and the cytokine, TNFα.
Non-CpG Methylation of the PGC-1α Promoter through DNMT3B Controls Mitochondrial Density. Cell Metabolism 10(3), 2009, Pages 189-198

3) Obesity is well known to increase MCP-1 levels and the finding that MCPIP is able to induce adipogenesis without involvement of PPARγ provides new mechanistic evidence for the role of MCP-1/CCR2 in obesity and type II diabetes.
MCP-1 (monocyte chemotactic protein-1)-induced protein, a recently identified zinc finger protein, induces adipogenesis in 3T3-L1 pre-adipocytes without peroxisome proliferator-activated receptor gamma. J Biol Chem. 2009 Oct 2;284(40):27620-8. Epub 2009 Aug 7.

4) Leptin was acting through a sequential activation of an AMPK → Akt → eNOS pathway leading to NO production..
Leptin-Stimulated Endothelial Nitric-Oxide Synthase via an Adenosine 5'-Monophosphate-Activated Protein Kinase/Akt Signaling Pathway Is Attenuated by Interaction with C-Reactive Protein. Endocrinology, August 2009, 150(8):3584–3593
↓
C-reactive protein suppresses insulin signaling in endothelial cells: role of spleen tyrosine kinase. Mol Endocrinol 2007, 21:564–573
↓
Syk Protective Against Breast Cancer

I do believe your lab will become bigger and bigger!!


6) Another thing about "metabolism ─ cancer", from the textbook "Drug Resistance in Cancer Cells" (2009)..

Ch7. Oxidative Stress and Drug Resistance in Cancer

[...] glucose deprivation was shown to rapidly induce cellular oxidative stress in the MCF-7 breast carcinoma cell line possibly through attenuation of ROS decomposition associated with the depletion of intracellular pyruvate (Spitz et al. 2000) [...]

Glucose deprivation-induced oxidative stress in human tumor cells. A fundamental defect in metabolism? Ann N Y Acad Sci. 2000;899:349-62.


[...] In tumor cell, HIF-1 plays a major role in metabolic switch that shunts glucose metabolites from mitochondria respiration to anaerobic glycolysis (the Warburg effect) (Lu et al. 2002). HIF activation not only promotes glycolysis but also attenuates mitochondrial respiration. The former occurs through the upregulation of genes encoding glucose transporter (GLUT), hexokinases, aldolase A, and lactate dehydrogenase A (LDH-A), the enzymes that convert pyruvate to lactate. Attenuation of mitochondrial respiration by HIF-1 is through the induction of PDK1 that inhibits pyruvate dehydrogenase, the enzyme that converts pyruvate into acetyl-CoA. Inhibition of pyruvate dehydrogenase prevents the entry of pyruvate to the TCA cycle and shunts pyruvate toward lactate formation through LDH (Kim et al. 2006b; Brahimi-Horn and Pouyssegur 2007). Owing to the role of mitochondrial as a major source of ROS production, it has been proposed that the increased glycolysis mediated by HIF facilitates cell survival through maintaining ATP production and preventing deleterious effect of ROS generated from mitochondrial respiration (Kim et al. 2006b). Recent study suggests that the increase in lactate production as a result of metabolic adaptation may play an important role in tumorigenesis (Fantin et al. 2006). [...]

Hypoxia-inducible factor 1 activation by aerobic glycolysis implicates the Warburg effect in carcinogenesis. J Biol Chem. 2002 Jun 28;277(26):23111-5.
→ Cited in: http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=link&linkname=pubmed_pubmed_citedin&uid=17046224&ordinalpos=1&log$=citedinpmcad1

HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia. Cell Metab. 2006 Mar;3(3):177-85.
→ PGC-1alpha is coupled to HIF-1alpha-dependent gene expression by increasing mitochondrial oxygen consumption in skeletal muscle cells. Proc Natl Acad Sci U S A. 2009 Feb 17;106(7):2188-93. back to energy expenditure.. so excited!!!!!　

Oxygen, a source of life and stress. FEBS Lett. 2007 Jul 31;581(19):3582-91.

Attenuation of LDH-A expression uncovers a link between glycolysis, mitochondrial physiology, and tumor maintenance. Cancer Cell. 2006 Jun;9(6):425-34.


Could you understand my excited and grateful about I can meet you and your collegemate Dr. Ronald Cortright from these references? Did you realize exactly the world you show me, give me?

We have anti-diabetic and anti-cancer drug discovery projects. Previously everybody assume these are two different worlds. After the FASEB conference, the small but potent Mitochondria links them together!!!!!!


That's all because of you are such a kind-hearted chairperson.

"教育，是一段生命影響生命的歷程。"

---

我們當初離不開的，最後也回不去

帶不走的，丟不掉的，我們擁有過好多、好多，多到在我心底一直滿溢出來疑問著我的決定。

---

只要你要，只要我有。

那些說給樹聽的話，嵌在樹的年輪裡，隨流年一點點長成參天的回憶；
而記憶像是倒在掌心的水，無論攤開還是握緊，總會從指縫中一點一滴流淌乾淨。

再美好也經不住遺忘，再悲傷也抵不過時間。

---

也許人最好的樣子就是靜一點、哪怕一個人生活

穿越一個又一個城市，走過一條又一條街道，仰望一片又一片天空，見證一場又一場別離。於是可以坦然說出，我‧不‧再‧那‧麼‧執‧著。

---

路是大地一道難癒合的傷口

成長的日子、總撕了皮連著肉。因此人生的每一步，都是隱隱的痛。

---

也許我們都該毫無怨言，因為活著就這麼一次、理應活的飛揚跋扈。

只是我還想知道，為什麼一瞬間、我們就在風裡長大了？那些花開，那些日落，那些單純清�酖�時光，那些明亮的青春以及年少的憂傷......

究竟是怎樣穿過我的身體、流淌的如此乾淨？

---

看不見雪的冬天，我們把它當春天好不好？

"I do like FASEB & FASEB SRC, also like this video. It remind me my first poster presentation experience at FASEB Summer Research Conference entitled, “The Physiological Basis for Obesity Therapeutics.” Haha~ "





"After I told them the most important thing the FASEB conference gave me is fearless,.

They say in my own world, the success programs are conventional and focus on "how to"- 1) Set a goal; 2) Work towards it; 3) Evaluate your progress; 4) Try again. But the world you show me, you let me know is "why to" and "why not to" success- 1) Ask questions; 2) Gain support; 3) Set up support system (people system); 4)Find true purpose in life.

They say you do an excellent mentoring job because you didn't ignore my subconscious or emotional roadblocks which might be preventing from achieving success. You pay attention to people: to what is imprisoning them; to what is frustrating them; to what is inhibiting them; to what is restraining them; to what is depriving them of a rich, energizing, intelligent, and forceful life. You take personal responsibility for the world you find yourself in.


I'm really very happy and grateful to meet you.

Research, to most students, is what their senior did or do. Research, to most students, is the job we've got to go to today. Research, to most RAs, is where we work. Research, to most RAs, is where we would least like to be if what we really want to be doing is having fun. You show me a different world and suggest something entirely different- Research is the most creative and challenging pursuit in which one can engage. It is also downright fun ─ if done right.."





收拾我所有的行李 搭乘末班希望班機 和信心一起旅行
這次要學習不逃避 揮別我所有的恐懼 勇敢地走下去

幸福在這一瞬間（幸福就在這一瞬間）
傷痛慢慢正開放（不用嘆息）
感謝有你 一路有你 風雨信心 多麼不容易
你我之間的默契（一點一點）
堆積美好的回憶（我會牢記）
感謝有你 一路有你 愛 讓一切變得更美麗

傷害我會忘記 明天我會繼續
夢想必定不要放棄 只要心相信 愛就永遠不止息

幸福在這一瞬間（幸福就在這一瞬間）
傷痛慢慢正開放（不用嘆息）
感謝有你 一路有你 風雨信心 多麼不容易
你我之間的默契（一點一點）
堆積美好的回憶（我會牢記）

感謝有你 一路有你 愛 讓一切變得更美麗
感謝有你 一路有你 愛 讓一切變得更美麗


The most important thing the FASEB conference gave me is fearless.
We do have very happy memory in there thus finally I realize what's mean "don't cry because it is over, smile because it happened."

Thus, good-bye, Chia-Yu. Good-bye, good-bye.
It's really really nice to meet you and you are my best friend at this lab. We have a real great time in here and in animal center. I'll think of you every step of the research way.

You cannot appreciate happiness unless you have known sadness too.
May your life soar on the wings of a dove in flight, after graduate from here, from DBPR.


My greetings, especially for you.

簡直就是太神奇了，神奇到一整個不可思議的地步，
當鼠小岩說出她要出國唸 PhD 的決定之後、得到的反應..

八月的美國行小岩已經覺得很神奇了，
禮拜一的中研院一日遊，結果更神奇 ─ 本來是要去找工作的，結果看著聽著小岩嘰嘰咕咕講完她的一切、大大大頭溫和但堅定地說，妳的未來不是在這裡、妳該接受獎學金去美國唸 PhD。下午的研討會沒想到還會遇到送咱們 CB1 knockout mice 的 Dr. Andreas Zimmer； 沒想到 Dr. Eric Yen present 時提出的兩種可能作用機制、第一種居然是小岩八月從 FASEB conference 回來後寫給他的； 沒想到 Eric 的老師 Dr. Jong-Young Yen 居然也和國外的大頭一樣幫忙用英文問著日本大頭篩糖尿病用藥的問題； 更沒想到 Eric 居然會說要跟 Dr. Zimmer 合作 ECS...

這些事也許真的很神奇，
但統統都比不上汶淇興奮到哭出來的真摯的祝福和薏婷婷留在桌上的小紙條和巧克力..


整隻呆掉的笨小岩。
但是，很感動。真的，真的真的謝謝。

PhD 的路很辛苦我知道，
但以後遇到困難的時候，我會提醒自己要一直一直記著 20091029 的下午。